Methods of oral immunotherapy

ABSTRACT

The present disclosure relates to improved oral immunotherapy methods for treating food allergies, and particularly peanut allergy. Biomarkers, such as a level of peanut-specific IgE and/or peanut-specific IgG4s are used by the methods described herein. Such methods include a method of treating a subject for a peanut allergy, methods of assessing the suitability of a treatment for a peanut allergy, a method of evaluating a symptom in a subject during the course of treatment of a peanut allergy, a method of monitoring treatment for a peanut allergy in a subject, a method of reducing the risk or incidence of an adverse event in a subject receiving treatment for a peanut allergy, a method of adjusting a dose of an allergenic peanut composition, and a method of assessing a likelihood of an allergic reaction that requires administration of epinephrine to a subject receiving treatment for a peanut allergy.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority benefit to U.S. Provisional ApplicationNo. 62/580,999, filed on Nov. 2, 2017, entitled “METHODS OF ORALIMMUNOTHERAPY”; U.S. Provisional Application No. 62/631,406, filed onFeb. 15, 2018, entitled “METHODS OF ORAL IMMUNOTHERAPY”; U.S.Provisional Application No. 62/637,903, filed on Mar. 2, 2018, entitled“METHODS OF ORAL IMMUNOTHERAPY”; and U.S. Provisional Application No.62/674,478, filed on May 21, 2018, entitled “METHODS OF ORALIMMUNOTHERAPY”; each of which are incorporated herein by reference forall purposes.

FIELD OF THE INVENTION

The present disclosure relates to methods for treating food allergies.

BACKGROUND OF THE INVENTION

Food allergy is an adverse reaction to food that is triggered by theimmune system. Food allergies affect 3% of the overall population and upto 4% to 6% of children (Sicherer, “Epidemiology of food allergy,” JAllergy Clin Immunol 2011; 127: 594-602). Allergic reactions to food maybe IgE mediated (causing immediate symptoms and possible anaphylaxis),non-IgE mediated (cell-mediated reactions with more delayed symptoms),or a combination of both. Previous reports suggest that over 80% ofpeanut-allergic patients have a peanut-specific IgE level of 100 kU/L orless. See, for example, Hourihane et al., Clinical characteristic ofpeanut allergy, Clinical and Experimental Allergy, vol. 27, no. 6, pp.634-639 (1997); Maloney et al., The use of serum-specific IgEmeasurements for the diagnosis of peanut, tree nut, and seed allergy,Journal of Allergy and Clinical Immunology, vol. 122, no. 1, pp. 145-151(2008); and Rance et al., Improved screening for peanut allergy by thecombined use of skin prick tests and specific IgE assays, Journal ofAllergy and Clinical Immunology, vol. 109, no. 6, pp. 1027-1033 (2002).Previous reports further suggest either that peanut-specific IgE has nocorrelation with reaction severity (see, for example, Clark et al.,Interpretation of tests for nut allergy in one thousand patients, inrelation to allergy or tolerance, Clinical and Experimental Allergy,vol. 33, no. 8, pp. 1041-1045 (2003) and Flinterman et al.,Determination of no-observed-adverse-effect levels and eliciting dosesin a representative group of peanut-sensitized children, Journal ofAllergy and Clinical Immunology, vol. 117, no. 2, pp. 448-454 (2006)),or that higher levels of peanut-specific IgE and/or increased epitopediversity are associated with severe reactions (see, for example,Vickery et al., Peanut oral immunotherapy modifies IgE and IgG4responses to major peanut allergens, Journal of Allergy and ClinicalImmunology, vol. 131, no. 1, pp. 128-134 (2013).

The current standard of care for treating food allergies includesidentifying the responsible food allergen and educating patients on howto avoid ingesting the food unknowingly and how to recognize and treatearly signs of an allergic reaction in case of accidental ingestion.Aside from avoidance of the offending food, there is no approveddisease-modifying therapy for treating food allergies at this time. Inrecent years, there is an increasing interest in oral immunotherapy(OIT) for the treatment of food allergy, and several clinical trialshave shown promising results. Immunotherapy, in general, entails gradualincreasing exposure to allergens in the hopes of desensitization(temporary loss of responsiveness due to continuous exposure) and/orpromoting tolerance (permanent immunologic nonresponse). Oralimmunotherapy involves the regular administration of small amounts ofallergen by the oral route to first induce desensitization, then overtime induce tolerance to the allergen. Although OIT appears to be apromising option for the treatment of food allergy, it is associatedwith high rates of adverse reactions (Skripak et al., “A randomized,double-blind, placebo-controlled study of milk oral immunotherapy forcow's milk allergy. J Allergy Clin Immunol. 2008; 122(6): 1154-1160;Jones et al., “Clinical efficacy and immune regulation with peanut oralimmunotherapy,” J Allergy Clin Immunol. 2009; 124(2):292-300; andVarshney et al., “Adverse reactions during peanut oral immunotherapyhome dosing,” J Allergy Clin Immunol. 2009; 124(6):1351-1352). Subjectsundergoing OIT on experience adverse reactions at an early stage of thetherapy, such as at the beginning of the therapy which is usuallyinitiated with very small amounts of the food allergen, or at a laterstage as the dose of the food allergen gradually increases.Consequently, subjects experiencing adverse reactions cannot bebenefited by oral immunotherapy alone.

Thus, there is a need in the art for improved methods for treating foodallergies. There is also need in the art for distinguishing betweensubjects with food allergies as likely or substantially less likely torespond favorably to OIT alone.

SUMMARY OF THE INVENTION

Described herein is a method of treating a subject for a peanut allergy,comprising administering to the subject at least one dose of anallergenic peanut composition, wherein the subject is selected fortreatment based on having a level of peanut-specific IgEs at or below apredetermined threshold. In some embodiments, the predeterminedthreshold for the level of peanut-specific IgEs is about 100 kU/L. Insome embodiments, the level of peanut-specific IgEs is determined priorto initiating treatment of the peanut allergy. In some embodiments, thedoes is administered to the subject as part of an oral immunotherapydosing regimen. In some embodiments, the dose is administered to thesubject during an initial escalation phase of the oral immunotherapydosing regimen. In some embodiments, the dose is administered to thesubject during an up-dosing phase of the oral immunotherapy dosingregimen. In some embodiments, the dose is administered to the subjectduring a maintenance phase of the oral immunotherapy dosing regimen. Insome embodiments, the method comprises receiving the level ofpeanut-specific IgEs. In some embodiments, the method comprisesmeasuring the level of peanut-specific IgEs.

Also described herein is a method of treating a subject for a peanutallergy, comprising administering to the subject at least one dose of anallergenic peanut composition, wherein the subject undergoes heightenedmonitoring for an allergenic reaction if a level of peanut-specific IgEsin the subject is above a predetermined threshold. In some embodiments,the predetermined threshold of the level of peanut-specific IgEs isabout 100 kU/L. In some embodiments, heightened monitoring comprises alonger clinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring for the allergic reaction. In someembodiments, active monitoring comprises measuring a heart rate, bloodpressure, respiratory rate, or blood oxygen. In some embodiments, theallergic reaction is hypersensitivity, anaphylaxis, a gastrointestinalsymptom, or eosinophilic esophagitis. In some embodiments, the dose isadministered to the subject as part of an oral immunotherapy dosingregimen. In some embodiments, the dose is administered to the subjectduring an initial escalation phase of the oral immunotherapy regimen. Insome embodiments, the dose is administered to the subject during anup-dosing phase of an oral immunotherapy regimen. In some embodiments,the dose is administered to the subject during a maintenance phase of anoral immunotherapy regimen.

In some embodiments of the methods described above, the method comprisesreceiving the level of peanut-specific IgEs. In some embodiments, themethod comprises measuring the level of peanut-specific IgEs.

Further described herein is a method of assessing the suitability of atreatment for a peanut allergy in a subject, comprising receiving alevel of peanut-specific IgEs in the subject; and assessing thesuitability of the treatment, wherein the subject having a level ofpeanut-specific IgEs at or below a predetermined threshold indicatesthat the treatment is suitable for the subject. In some embodiments, thepredetermined threshold of the level of peanut-specific IgEs is about100 kU/L. In some embodiments, the treatment is an oral immunotherapydosage regimen. In some embodiments, the method comprises initiatingadministration of the oral immunotherapy dosage regimen to the subject.In some embodiments, initiating administration of the oral immunotherapydosage regimen to the subject comprises administering an initialescalation phase of the oral immunotherapy regimen to the subject. Insome embodiments, receiving the level of the peanut-specific IgEs in thesubject comprises measuring the level of peanut-specific IgEs in thesubject. These methods are preferably performed in vitro.

Also described herein is a method of evaluating a symptom in a subjectduring the course of treatment of a peanut allergy, comprising receivinga level of peanut-specific IgEs in the subject having an adverse event;and determining whether the symptom is related to the treatment, whereina level of peanut-specific IgEs at or below a predetermined thresholdindicates that the adverse event is not caused by the treatment. In someembodiments, the level of peanut-specific IgE is determined prior toinitiating the course of treatment. In some embodiments, the level ofpeanut-specific IgE is determined during the course of treatment. Insome embodiments, the level of peanut-specific IgE is determined whenthe subject is symptomatic. In some embodiments, the predeterminedthreshold of the level of peanut-specific IgEs is about 100 kU/L. Insome embodiments, the treatment is an oral immunotherapy dosage regimen.In some embodiments, the symptom is a gastrointestinal symptom. In someembodiments, the gastrointestinal symptom is vomiting or abdominal pain.In some embodiments, the method comprises delaying a dose increaseduring an up-dosing phase of the treatment if the symptom is determinedto be related to the treatment. In some embodiments, the methodcomprises reducing or delaying a dose of an allergenic peanutcomposition administered to the subject if the symptom is determined tobe related to the treatment. In some embodiments, the method comprisesterminating the treatment if the symptom is determined to be related tothe treatment. In some embodiments, receiving the level ofpeanut-specific IgEs comprises measuring the level of peanut-specificIgEs. These methods are preferably performed in vitro.

Further described herein is a method of monitoring treatment for apeanut allergy in a subject, comprising measuring a level ofpeanut-specific IgEs in the subject during the course of treatment. Insome embodiments, the treatment is an oral immunotherapy dosage regimen.In some embodiments, the method comprises reducing or delaying a dose ofan allergenic peanut composition if the level of peanut-specific IgEs isabove a predetermined threshold. In some embodiments, the methodcomprises delaying a dose increase during an up-dosing phase of thetreatment if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the method comprises terminating thetreatment if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the method comprises increasing the doseif the level of peanut-specific IgEs is at or below a predeterminedthreshold. In some embodiments, the predetermined threshold is about 100kU/L. In some embodiments, the level of peanut-specific IgEs is measuredfollowing an initial escalation phase of the treatment. In someembodiments, the method comprises the level of peanut-specific IgEs ismeasured during an up-dosing phase of the treatment. These methods arepreferably performed in vitro.

Also described herein is a method of reducing the risk or incidence ofan adverse event in a subject receiving treatment for a peanut allergy,comprising: receiving a level of peanut-specific IgEs in the subject;and reducing a dose, delaying a dose, or delaying an increase of a doseof an allergenic peanut composition if the level of peanut-specific IgEsis above a predetermined threshold. In some embodiments, the treatmentis oral immunotherapy. In some embodiments, the predetermined level ofthe peanut-specific IgEs is about 100 kU/L. In some embodiments,receiving the level of the peanut-specific IgEs in the subject comprisesmeasuring the level of peanut-specific IgEs in the subject. In someembodiments, the adverse event is an allergic reaction. In someembodiments, the method comprises reducing the dose of the allergicpeanut composition if the level of peanut-specific IgEs is above thepredetermined threshold. In some embodiments, the dose of the allergenicpeanut composition is reduced during an up-dosing phase of the therapy.In some embodiments, the method comprises delaying the dose of theallergic peanut composition if the level of peanut-specific IgEs isabove the predetermined threshold. In some embodiments, the methodcomprises delaying the increase of the dose of the allergic peanutcomposition during an up-dosing phase of the therapy if the level ofpeanut-specific IgEs is above the predetermined threshold. In someembodiments, the method comprises administering the dose to the subject.

Further described herein is a method of adjusting a dose of anallergenic peanut composition, comprising: administering a first dose ofthe allergenic peanut composition to a subject with a peanut allergy;receiving a level of peanut-specific IgEs in the subject afteradministration of the first dose; and administering a second dose of theallergenic peanut composition to the subject, wherein the second dose isbased on the first dose and the level of peanut-specific IgEs in thesubject. In some embodiments, the second dose is lower than the firstdose if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the administration of the second dose isdelayed if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the second dose is the same as the firstdose if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the second dose is increased relative tothe first dose if the level of peanut-specific IgEs is at or below thepredetermined threshold. In some embodiments, the predeterminedthreshold is about 100 kU/L. In some embodiments, receiving the level ofpeanut-specific IgEs in the subject comprises measuring the level ofpeanut-specific IgEs.

Also described herein is a method of assessing a likelihood of anallergic reaction that requires administration of epinephrine to asubject receiving treatment for a peanut allergy, wherein the treatmentcomprises administration of at least one dose of an allergenic peanutcomposition, the method comprising: receiving a level of peanut-specificIgEs in the subject; and assessing the likelihood of an allergicreaction that requires administration of epinephrine to the patient,wherein a level of peanut-specific IgEs at or below a predeterminedthreshold indicates a reduced likelihood of an allergic reaction thatrequires administration of epinephrine during treatment, and wherein alevel of peanut-specific IgEs above the predetermined thresholdindicates an increased likelihood of an allergic reaction that requiresadministration of epinephrine during treatment. In some embodiments, themethod further comprises administering to the subject one or more dosesof an allergenic peanut composition if the level of peanut-specific IgEsis at or below the predetermined threshold. In some embodiments, thepredetermined threshold of the level of peanut-specific IgEs is about100 kU/L. In some embodiments, the treatment is an oral immunotherapydosing regimen. In some embodiments, the method comprises recommendingto the subject that the subject have immediate access to at least twodoses of injectable epinephrine for treatment of the allergic reactionif the subject has a level of peanut-specific IgEs above thepredetermined threshold. In some embodiments, each dose of epinephrineis about 0.15 mg of injectable epinephrine if the subject weighs lessthan about 30 kilograms, or about 0.3 mg of injectable epinephrine ifthe subject weighs about 30 kilograms or more.

In some embodiments of the methods described above, the subject is ahuman. In some embodiments, the subject is about 17 years of age oryounger. In some embodiments, is about 4 years of age to about 17 yearsof age.

In some embodiments of the methods described above, the method comprisesmeasuring the level of peanut-specific IgEs in the subject prior toinitiating treatment for the peanut allergy. In some embodiments, thelevel of peanut-specific IgEs in the subject is a level determined priorto initiating treatment of the peanut allergy. In some embodiments, thelevel of peanut-specific IgEs in the subject is a level determinedduring the course of treatment.

In some embodiments of the methods described above, the level ofpeanut-specific IgEs or the level of peanut-specific IgG4 corresponds toa level as measured by a fluorescence enzyme immunoassay auto-analyzer.In some embodiments, the level of peanut-specific IgEs or the level ofpeanut-specific IgG4 is measured by a fluorescence enzyme immunoassayauto-analyzer. In some embodiments, the level is measured in vitro.

Also described herein is an allergenic peanut composition for use intreating a subject for a peanut allergy, wherein (as discussed above):the subject is selected for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; the subjectundergoes heightened monitoring for an allergenic reaction if a level ofpeanut-specific IgEs in the subject is above a predetermined threshold;a level of peanut-specific IgEs in the subject is measured during thecourse of treatment and, optionally, a dosage of the composition isreduced or delayed, or an increase in dosage is delayed, if the level ofpeanut-specific IgEs is above a predetermined threshold; and/or a firstand a second dose of the composition are administered, wherein thesecond dose is based on the first dose and the level of peanut-specificIgEs in the subject.

Also described herein is the use of an allergenic peanut composition inthe manufacture of a medicament for treating a subject for a peanutallergy, wherein (as discussed above): the subject is selected fortreatment based on having a level of peanut-specific IgEs at or below apredetermined threshold; the subject undergoes heightened monitoring foran allergenic reaction if a level of peanut-specific IgEs in the subjectis above a predetermined threshold; a level of peanut-specific IgEs inthe subject is measured during the course of treatment and, optionally,a dosage of the composition is reduced or delayed, or an increase indosage is delayed, if the level of peanut-specific IgEs is above apredetermined threshold; a first and a second dose of the compositionare administered, wherein the second dose is based on the first dose andthe level of peanut-specific IgEs in the subject.

In some embodiments of the methods described above, the subject is ahuman.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a post-hoc patient cohort preliminary analysis from aphase 2 clinical trial of an oral immunotherapy (OIT) for the treatmentof a peanut allergy.

FIG. 1B shows considerations for patient cohorts in the treatment ofpeanut allergy by OIT by peanut-specific IgE levels after preliminaryanalysis.

FIG. 1C shows additional post-hoc patient cohort preliminary analysisfrom a phase 2 clinical trial of an oral immunotherapy (OIT) for thetreatment of a peanut allergy.

FIG. 2 illustrates an exemplary treatment protocol for treating a peanutallergy patient with oral immunotherapy (OIT).

FIG. 3 shows the median amount of peanut protein tolerated in entry andexit peanut challenges for the intent-to-treat population for an oralimmunotherapy trial and a placebo.

FIG. 4A and FIG. 4B show the symptom severity observed at each indicatedpeanut protein dose during an exit peanut challenge for a 4-17 year-oldcompleter population of an oral immunotherapy for peanut allergytreatment (FIG. 4B) and a placebo (FIG. 4A). The number of peoplepassing the indicated peanut protein dose are indicated by a blackdiamond.

FIG. 5 shows the percentage of subjects in oral immunotherapy for apeanut allergy and placebo arms that tolerate a 600 mg dose of peanutprotein during the exit double blind, placebo controlled food challenge(DBPCFC), broken down into the age groups 4-11, 12-17, and 18-55 yearold subjects.

FIG. 6A shows the average level of peanut-specific IgE for the oralimmunotherapy and placebo arms at start (baseline), at the end of theup-dosing phase, and at study exit

FIG. 6B shows the average peanut-specific IgE to IgG4 ratio for the oralimmunotherapy and placebo arms at start (baseline), at the end of theup-dosing phase, and at study exit.

FIG. 6C shows the reaction to the skin prick test as measured by meanwheal diameter above negative control for oral immunotherapy and placeboarms at start (baseline), at the end of the up-dosing phase, and atstudy exit.

FIG. 6D shows that peanut-specific IgG4 increased during the course ofthe study for the OIT recipients, whereas peanut-specific IgG4 levelsremained approximately stable for recipients of the placebo formulation.

DESCRIPTION OF THE INVENTION

The invention disclosed herein provides in various embodiments improvedmethods for treating a subject suffering from an allergy such as a foodallergy. The inventors have found that patients suffering from anallergy such as a food allergy can be divided into sub-populations orsub-groups of patients as likely or unlikely to respond favorably tooral immunotherapy (OIT) with escalating doses of the food allergenbased on the levels of one or more biomarkers. The patients can then betreated with OIT alone if they are likely to respond favorably to theoral administration of escalating doses of the food allergen. Thepatients who are unlikely to respond favorably to the oraladministration of escalating doses of the food allergen can be treatedwith OIT in a modified manner to as to improve the likelihood ofsuccessfully completing OIT. For example, such a method can compriseadministering the allergen in an OIT therapy in combination with anothertherapeutic agent such as an antagonist of one or more immunologicmediators of allergy, so as to improve their likelihood of respondingfavorably to OIT.

For instance, the inventors have found that subjects suffering from apeanut allergy can be divided at least into two groups: i) subjectslikely to respond favorably to oral administration of escalating dosesof peanut allergens and ii) subjects substantially less likely torespond favorably to oral administration of escalating doses of peanutallergens.

It has been found that the level of peanut-specific IgEs in a subjectcan indicate whether the subject is a good candidate for low-risktreatment of a peanut allergy. Patients with a level of peanut-specificIgEs at or below a predetermined threshold (such as about 100 kU/L) canbe considered low-risk for an adverse reaction (such as anaphylaxis oreosinophilic esophagitis (EoE)) caused by the treatment. In someembodiments, subjects with a level of peanut-specific IgEs above thepredetermined threshold are still administered treatment for the peanutallergy, although in such circumstances it is generally preferred thatthe subject undergoes heightened monitoring for an allergic reaction orthat up-dosing of the allergenic peanut composition be limited or dosingreduced, as further explained herein.

The level of peanut-specific IgEs can also be used to evaluate anadverse event in a subject during the course of treatment of a peanutallergy. The symptoms of an allergic reaction are often similar to morebenign or otherwise unrelated symptoms. For example, certaingastrointestinal symptoms in a subject, such as vomiting or abdominalpain, may be caused by an allergic reaction to an allergenic compositionadministered to the patient, or may be caused by an unrelated viralinfection. The level of peanut-specific IgEs in the subject can be usedto help indicate the cause of the symptoms. For example, in someembodiments, if the subject has a level of peanut-specific IgEs above apredetermined threshold (such as about 100 kU/L), the likelihood thatthe symptom is due to an allergic reaction to the peanut allergytreatment is heightened compared to if the level of the peanut-specificIgEs in the subject is at or below the predetermined threshold. If thesubject has a level of peanut specific IgEs at or below thepredetermined threshold, the likelihood that the symptom is due to anallergic reaction to the peanut allergy treatment is lessened comparedto if the level of the peanut-specific IgEs in the subject is above thepredetermined threshold. If the symptoms are found to be due to thetreatment for peanut allergy, adjustments to the treatment can be madeor the treatment a can be terminated. Adjustments the treatment mayinclude reducing a dose or maintaining a dose instead of raising a doseduring an up-dosing phase of treatment.

In some embodiments, the level of peanut-specific IgEs in the subject isused to assess the suitability of a treatment for a peanut allergy in asubject, or for assessing the suitability of the subject for treatmentof a peanut allergy by immunotherapy (for example, oral immunotherapy).The method of assessing the suitability of a treatment for a peanutallergy in a subject can include receiving a level of peanut specificIgEs in the subject; and assessing the suitability of the treatment,wherein the subject having a level of peanut-specific IgEs at or below apredetermined threshold indicates that the treatment is suitable for thesubject. The method of assessing the suitability of a subject for thetreatment of a peanut allergy can include receiving a level of peanutspecific IgEs in the subject; and assessing the suitability of thesubject for the treatment, wherein the subject having a level ofpeanut-specific IgEs at or below a predetermined threshold indicatesthat the subject is suitable for the treatment. Additionally, as furtherdescribed herein, the risk or incidence of an adverse event in a subjectreceiving treatment for a peanut allergy can be reduced by receiving alevel of peanut-specific IgEs in the subject; and reducing a dose,delaying a dose, or delaying an increase of a dose of an allergenicpeanut composition if the level of peanut-specific IgEs is above apredetermined threshold.

The level of peanut-specific IgEs can also be used to evaluate a symptomin a subject during the course of treatment for a peanut allergy. Forexample, a method of evaluating a symptom in a subject during the courseof treatment of a peanut allergy can include receiving a level ofpeanut-specific IgEs in the subject having an adverse event; anddetermining whether the symptom is related to the treatment, wherein alevel of peanut-specific IgEs at or below a predetermined thresholdindicates that the adverse event is not caused by the treatment.

As further described herein, the level of peanut-specific IgEs can beused to assess a likelihood of an allergic reaction that requiresadministration of epinephrine to a subject receiving treatment for apeanut allergy. For example, a method of assessing a likelihood of anallergic reaction that requires administration of epinephrine to asubject receiving treatment for a peanut allergy, wherein the treatmentcomprises administration of at least one dose of an allergenic peanutcomposition, can include receiving a level of peanut-specific IgEs inthe subject; and assessing the likelihood of an allergic reaction thatrequires administration of epinephrine to the patient, wherein a levelof peanut-specific IgEs at or below a predetermined threshold indicatesa reduced likelihood of an allergic reaction that requiresadministration of epinephrine during treatment, and wherein a level ofpeanut-specific IgEs above the predetermined threshold indicates anincreased likelihood of an allergic reaction that requiresadministration of epinephrine during treatment.

In certain embodiments, the invention provides methods of treating asubject suffering from a food allergy who is more likely to respondfavorably to oral immunotherapy comprising identifying a subject who ismore likely to respond favorably to oral immunotherapy and administeringto the subject more likely to respond favorably, at least one dose ofthe food allergen to the subject according to a dosing schedule. Inother embodiments, the invention provides methods of treating a subjectsuffering from a food allergy who is significantly less likely torespond favorably to oral immunotherapy alone, said method comprisingidentifying the subjects who are significantly less likely to respondfavorably to oral immunotherapy, administering at least one dose of thefood allergen to the subject according to a dosing schedule andconcomitantly administering a second therapeutic agent, for example atherapeutic agent which can improve the response of the subject to oralimmunotherapy. The invention further provides methods of diagnosing oridentifying a subject suffering from food allergy as likely, unlikely,or substantially less likely to respond favorably to oral immunotherapyalone based on one or more biomarkers.

Receiving a level of IgEs (such as a level of peanut-specific IgEs) caninclude any method of obtaining the IgE level. For example, in someembodiments, the level of IgE is received from a clinical laboratorythat measured the IgE level. In some embodiments, the level of IgE isreceived by measuring the IgE level.

The level of peanut-specific IgEs can be measured from a patient serumsample (i.e., to measure a serum level of peanut-specific IgEs) or froma patient plasma sample (i.e., to measure a plasma level ofpeanuts-specific IgEs). Whole blood can be drawn from the patient, andthe serum or plasm can be isolated from the whole blood using knownmethods. The level of the IgEs, including the level of total IgE, thelevel of peanut-specific IgEs, or the level of antigen-specific IgEs canbe measured, for example, using a quantitative immunoassay.

Quantitative immunoassays are known in the art, and can include, but arenot limited to, an enzyme-linked immunosorbent assay (ELISA); analkaline phosphatase immunoassay auto-analyzer, such as an IMMULITE®system (Siemens Healthcare Diagnostics, Erlangen, Germany); aradioallergosorbent test (RAST), or a fluoroenzyme immunoassayauto-analyzer, such as the ImmunoCAP® system (Thermo FisherScientific/Phadia, Uppsala, Sweden). A fluorescence enzyme immunoassay(FEIA) auto-analyzer (e.g., ImmunoCAP® system) is a preferred technique,although other techniques may be reliably used. For example, anothertechnique may be used as the level of antibody (e.g., IgE or IgG4)determined by that technique may be normalized to a measurement by afluorescence enzyme immunoassay auto-analyzer. That is, a level ofantibody (e.g., IgE or IgG4) can be determined by a technique, and cancorrespond to a level as measured by a fluorescence enzyme immunoassayauto-analyzer. The level of the biomarker (e.g., level ofpeanut-specific IgE and/or peanut-specific IgG4) is preferablydetermined in vitro.

As used herein, the singular forms “a,” “an,” and “the” include theplural references unless the context clearly dictates otherwise.

Reference to “about” a value or parameter herein includes (anddescribes) variations that are directed to that value or parameter perse. For example, description referring to “about X” includes descriptionof “X”.

It is understood that aspects and variations of the invention describedherein include “consisting” and/or “consisting essentially of” aspectsand variations.

The term “receiving” a level or value is understood to encompass anymethod of obtaining the level or value, for example by measuring thelevel or value, or by receiving the level or value from another party orentity that measures the level or value.

When a range of values is provided, it is to be understood that eachintervening value between the upper and lower limit of that range, andany other stated or intervening value in that stated range, isencompassed within the scope of the present disclosure. Where the statedrange includes upper or lower limits, ranges excluding either of thoseincluded limits are also included in the present disclosure.

The section headings used herein are for organization purposes only andare not to be construed as limiting the subject matter described.Various modifications to the described embodiments will be readilyapparent to those persons skilled in the art and the generic principlesherein may be applied to other embodiments. Thus, the present inventionis not intended to be limited to the embodiment shown but is to beaccorded the widest scope consistent with the principles and featuresdescribed herein.

The disclosures of all publications, patents, and patent applicationsreferred to herein are each hereby incorporated by reference in theirentireties. To the extent that any reference incorporated by referenceconflicts with the instant disclosure, the instant disclosure shallcontrol.

The following provides an exemplary method of a quantitative immunoassayto determine the level of peanut-specific IgEs in a subject. Whole bloodcan be withdrawn from the subject, and plasma or serum can be isolatedfrom the whole blood. Peanut allergens from a peanut protein extract canbe bound to a solid phase, such as a cellulose derivative with a highallergen binding capacity while maintaining their native structure. Theisolated plasma or serum from the subject is introduced to the solidphase, where subject IgE molecules specific for the immobilized peanutallergens are pulled out of solution. Non-specific IgE molecules arethen washed away. Antibodies against IgE (for example, an anti-human IgEantibody) that includes a signal-emitting moiety is added to the solidphase and incubated to allow the anti-IgE antibodies to bind to thepeanut-specific IgEs bound to the surface. Unbound anti-IgE antibody canbe washed away. The remaining immobilized complex comprising theallergen, specific IgE, and labeled anti-IgE antibody is incubated witha signal-developing agent. After stopping the signal-developingreaction, the intensity of the signal of the eluate is measured. Signal,such as fluorescence generated from a fluorophore, is correlated withthe IgE level. Serial dilution may be carried out on the subject plasmaor serum before the assay to bring the IgE concentration into the linearrange of detection for any given assay. The intensity of signal, e.g.,fluorescence, may be correlated to peanut-specific IgE serumconcentration by comparison with a known control. The level ofpeanut-specific IgEs may be reported, such as to the subject or aclinician, which receives the level of peanut-specific IgEs.

In one embodiment, subjects likely to respond favorably to oraladministration of escalating doses of the peanut allergens have apeanut-specific serum IgE level of less than about 100 kU/L. In anotherembodiment, subjects likely to respond favorably to oral administrationof escalating doses of the peanut allergens have a peanut-specific serumIgE level of about 0.35 kU/L to about 99 kU/L. In yet anotherembodiment, subjects likely to respond favorably to oral administrationof escalating doses of the peanut allergens have a peanut-specific serumIgE level of about 0.35 kU/L to about 50 kU/L, about 0.35 kU/L to about55 kU/L, about 0.35 kU/L to about 60 kU/L, about 0.35 kU/L to about 65kU/L, about 0.35 kU/L to about 70 kU/L, about 0.35 kU/L to about 75kU/L, about 0.35 kU/L to about 80 kU/L, about 0.35 kU/L to about 85 kU/Labout 0.35 kU/L to about 90 kU/L about 0.35 kU/L to about 95 kU/L, about0.35 kU/L to about 99 kU/L, or about 0.35 kU/L to about 100 kU/L,including values and ranges therebetween.

In yet another embodiment, subjects likely to respond favorably to theoral administration of escalating doses of the peanut allergens have apeanut-specific serum IgE level of about 0.35 kU/L to about 125 kU/L,about 0.35 kU/L to about 150 kU/L, about 0.35 kU/L, to about 175 kU/L,about 0.35 kU/L to about 200 kU/L, about 0.35 kU/L to about 225 kU/L,about 0.35 kU/L to about 250 kU/L, about 0.35 kU/L to about 275 kU/L,about 0.35 kU/L to about 300 kU/L, about 0.35 kU/L to about 325 kU/L,about 0.35 kU/L to about 350 kU/L, about 0.35 kU/L to about 375 kU/L,about 0.35 kU/L to about 400 kU/L, about 0.35 kU/L to about 425 kU/L, orabout 0.35 kU/L to about 450 kU/L, including values and rangestherebetween. In still another embodiment, subjects likely to respondfavorably to the oral administration of escalating doses of the peanutallergens have a peanut-specific serum IgE level of less than about 100kU/L to about 125 kU/L, less than about 100 kU/L to about 150 kU/L, lessthan about 100 kU/L to about 175 kU/L, less than about 100 kU/L to about200 kU/L, less than about 200 kU/L to about 250 kU/L, less than about200 kU/L to about 300 kU/L, less than about 300 kU/L to about 350 kU/L,or less than about 300 kU/L to about 400 kU/L, including values andranges therebetween.

In one embodiment, subjects unlikely to respond favorably to oraladministration of escalating doses of the peanut allergens have apeanut-specific serum IgE level of about 100 kU/L or more. In anotherembodiment, subjects unlikely to respond favorably to oraladministration of escalating doses of the peanut allergens have apeanut-specific serum IgE level of about 70 kU/L, about 75 kU/L, about80 kU/L, about 85 kU/L, about 90 kU/L, about 95 kU/L, about 100 kU/L,about 125 kU/L, about 150 kU/L, about 175 kU/L, about 200 kU/L, about225 kU/L, about 250 kU/L, about 275 kU/L, about 300 kU/L, about 325kU/L, about 350 kU/L, about 375 kU/L about 400 kU/L, or more, includingvalues and ranges therebetween.

According to one aspect of the invention, treating subjects likely torespond favorably to oral administration of escalating doses of thepeanut allergens according to the methods of the invention would resultin as success rate of at least about 80%, at least about 85%, at leastabout 90%, at least about 95% or about 100%, including valuestherebetween. That is, in one embodiment, at least about 80%, at leastabout 85%, at least about 90%, at least about 95% or about 100% of thesubjects likely to respond favorably to the oral administration ofescalating doses of the peanut allergens, when treated according to themethods of the invention would not develop one or more allergicreactions or symptoms after consuming peanuts.

The terms “patient” and “subject” are used interchangeably throughoutthis disclosure. In some embodiments, the subject is a human subject.

An action “based on” a factor is well-understood to refer to an actionthat results from taking into account the factor. The factor need not bean exclusive factor, or even a primary factor, for determining whetherand/or how the action occurs. Accordingly, the phrase “action X based onfactor Y” means that factor Y is taken into account when determiningwhether and/or how the action X should or would be performed (orconversely, not performed). The factor need not be an exclusive factorin determining whether or how action X should be performed, and may be,but need not be, a primary or secondary factor taken into account.Various types of actions are described herein, such as methodsadministering a dose comprising an allergenic composition to a subjectand methods of identifying a subject suitable for the treatment of apeanut allergy. Various types of factors, such as a level of IgE in thesubject, particularly in reference to a threshold, are also described.

The invention provides methods of treating a subject suffering from asfood allergy, comprising orally administering at least one dose of atleast one allergen to the subject according to a dosing schedule,wherein the subject is likely to respond favorably to the oraladministration of the food allergen.

In various embodiments, the subject likely to respond favorably to theoral administration of the food allergen has the food allergen-specificserum IgE levels of about 0.35 kU/L to about 0.69 kU/L, about 0.70 kU/Lto about 3.49 kU/L, about 3.50 kU/L to about 17.4 kU/L, about 17.5 kU/Lto about 49.9 kU/L, about 50 kU/L to about 99.9 kU/L, about 0.35 kU/L toabout 17.4 kU/L, about 0.35 kU/L to about 20 kU/L, about 0.35 kU/L toabout 25 kU/L, about 0.35 kU/L to about 30 kU/L, about 0.35 kU/L toabout 35 kU/L, about 0.35 kU/L to about 40 kU/L, about 0.35 kU/L toabout 45 kU/L, about 0.35 kU/L to about 50 kU/L, about 0.35 kU/L toabout 55 kU/L, about 0.35 kU/L to about 60 kU/L, about 0.35 kU/L toabout 65 kU/L, about 0.35 kU/L to about 70 kU/L, about 0.35 kU/L toabout 75 kU/L, about 0.35 kU/L to about 80 kU/L, about 0.35 kU/L toabout 85 kU/L, about 0.35 kU/L to about 90 kU/L, about 0.35 kU/L toabout 95 kU/L, or about 0.35 kU/L to about 99 kU/L, including values andranges therebetween.

In yet another embodiment, subjects likely to respond favorably to theoral administration of escalating doses of the food allergen have a foodallergen-specific serum IgE level of about 0.35 kU/L to about 125 kU/L,about 0.35 kU/L to about 150 kU/L, about 0.35 kU/L to about 175 kU/L,about 0.35 kU/L to about 200 kU/L, about 0.35 kU/L to about 225 kU/L,about 0.35 kU/L to about 250 kU/L, about 0.35 kU/L to about 275 kU/L,about 0.35 kU/L to about 300 kU/L, about 0.35 kU/L to about 325 kU/L,about 0.35 kU/L to about 350 kU/L, about 0.35 kU/L to about 375 kU/L,about 0.35 kU/L to about 400 kU/L, about 0.35 kU/L to about 425 kU/L, orabout 0.35 kU/L to about 450 kU/L, including values and rangestherebetween.

In still another embodiment, subjects likely to respond favorably to theoral administration of escalating doses of the food allergen have a foodallergen-specific serum IgE level of less than about 100 kU/L to about125 kU/L, less than about 100 kU/L to about 150 kU/L, less than about100 kU/L to about 175 kU/L, less than about 100 kU/L to about 200 kU/L,less than about 200 kU/L to about 250 kU/L, less than about 200 kU/L toabout 300 kU/L, less than about 300 kU/L to about 350 kU/L, or less thanabout 300 kU/L to about 400 kU/L, including values and rangestherebetween.

The invention provides methods of treating a subject suffering from afood allergy, comprising orally administering at least one dose of atleast one allergen to the subject according to a dosing schedule, andconcomitantly administering another therapeutic agent; wherein thesubject is unlikely to respond favorably to the oral administration ofthe food allergen.

In one embodiment, the subject unlikely to respond favorably to the oraladministration of the food allergen has the food allergen-specific serumIgE levels of about 17 kU/L or more. In various other embodiments, thesubject unlikely to respond favorably to the oral administration of thefood allergen has the food allergen-specific serum IgE levels of about50 kU/L or more, about 55 kU/L or more, about 60 kU/L or more, about 65kU/L or more, about 70 kU/L or more, about 75 kU/L or more, about 80kU/L or more, about 85 kU/L or more, about 90 kU/L or more, about 95kU/L or more, about 100 kU/L or more, about 125 kU/L or more, about 150kU/L or more, about 175 kU/L or more, about 200 kU/L or more, about 225kU/L or more, about 250 kU/L or more, about 275 kU/L or more, about 300kU/L or more, about 325 kU/L or more, about 350 kU/L or more, about 375kU/L or more, or about 400 kU/L or more, including values and rangestherebetween.

According to certain aspects of the invention, patients suffering from afood allergy can be classified as likely or unlikely to respondfavorably to OIT with escalating doses of the food allergen based on thelevels of one or more biomarkers. The biomarkers that could be used todistinguish the patient population as likely or unlikely to respondfavorably to OIT include, but are not limited to, total IgE, foodallergen-specific IgEs, food allergen-specific IgG4, cell surfacemarkers on immune cells (e.g. lymphocytes, monocytes, basophils,eosinophils), ratio of IgG/IgE, ratio of food allergen-specificIgE/IgG4, age, and gender.

For instance, patients suffering from a peanut allergy can be classifiedas likely or unlikely to respond favorably to OIT with escalating dosesof peanut allergens based on the levels of one or more biomarkersincluding, but not limited to, total IgE, peanut-specific IgEs,peanut-specific IgG4, component-resolved peanut IgE (e.g., Arah1-specific IgE, Ara h2-specific IgE, Ara h3-specific IgE, Arah8-specific IgE, Ara h9-specific IgE), cell surface markers on immunecells (e.g. lymphocytes, monocytes, basophils, eosinophils), ratio ofIgG/IgE, ratio of peanut-specific total IgE/IgG4, ratio of individualpeanut component-specific IgE/IgG4, age, and gender.

According to one aspect, a subject suffering from a food allergy who isunlikely to respond favorably to the oral administration of the foodallergen is treated by orally administering at least one dose of atleast one allergen to the subject according to a dosing schedule, andconcomitantly administering another therapeutic agent. In oneembodiment, the other therapeutic agent is an antagonist of one or moreimmunological mediators of allergy.

For instance, the other therapeutic agent could be, but is not limitedto, an IgE antagonist such as Omalizumab (Xolair), IL-4 antagonist, IL-5antagonist, IL-13 antagonist, IL-33 antagonist and combinations thereof.Exemplary IgE antagonists include ligelizumab (Phase 2). Exemplary IL-5antagonists include Cinquil/reslizumab (approved), Nucala/mepolizumab(approved), and benralizumab (Phase 3). Exemplary IL-4/IL-13 antagonistsinclude dupilumab (Phase 3) and SAR156597 (Phase 2). Exemplary IL-13antagonists include lebrikizumab (Phase 3) and tralokinumab (Phase 3).Exemplary IL-33 antagonists include AMG 282 (Phase 1) and ANB020 (Phase1).

The other therapeutic agent can be administered concomitantly, but inseparate formulations, or sequentially. In some embodiments, concomitantadministration includes prior administration, for instance,administration of the other therapeutic agent within the range of about60 minutes, 50 minutes, 40 minutes, 30 minutes, 20 minutes, 10 minutes,or 5 minutes prior to administration of the allergen. In certainembodiments, concomitant administration includes prior administration,for instance, administration of the other therapeutic agent about 1week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks,about 11 weeks, about 12 weeks, about 13 weeks, about 14 weeks, about 15weeks, and/or about 16 weeks, including ranges therebetween, prior toadministration of the allergen. In other embodiments, concomitantadministration includes prior administration, for instance,administration of the other therapeutic agent about one week, about twoweeks, about one month, about two months, about 3 months, and/or aboutfour months, including ranges therebetween, prior to administration ofthe allergen.

The invention further provides methods of diagnosing a subject sufferingfrom a food allergy as likely or unlikely to respond favorably to theoral administration of the food allergen based on the levels of one ormore biomarkers in the subject.

For instance, the invention provides a method of diagnosing a subjectsuffering from a food allergy as likely or unlikely to respond favorablyto the oral administration of peanut allergens comprising measuring thelevel of peanut-specific serum IgE in the subject and diagnosing thesubject as likely to respond favorably to the oral administration ofpeanut allergens if the subject as the peanut-specific serum IgE levelbelow a particular threshold or diagnosing the subject as unlikely torespond favorably to the oral administration of peanut allergens if thesubject has the peanut-specific serum IgE level above a particularthreshold.

In one embodiment, a subject having a peanut allergy is diagnosed aslikely to respond favorably to the oral administration of peanutallergens if the subject has the peanut-specific serum IgE level ofabout 0.35 kU/L to about 17.4 kU/L, about 0.35 kU/L to about 20 kU/L,about 0.35 kU/L to about 25 kU/L, about 0.35 kU/L to about 30 kU/L,about 0.35 kU/L to about 35 kU/L, about 0.35 kU/L to about to about 40kU/L, about 0.35 kU/L to about 45 kU/L, about 0.35 kU/L to about 50kU/L, about 0.35 kU/L, to about 55 kU/L, about 0.35 kU/L to about 60kU/L, about 0.35 kU/L to about 65 kU/L, about 0.35 KU/L to about 70kU/L, about 0.35 kU/L to about 75 kU/L, about 0.35 kU/L to about 80kU/L, about 0.35 kU/L to about 85 kU/L, about 0.35 kU/L to about 90kU/L, about 0.35 kU/L to about 95 kU/L, about 0.35 kU/L to about 99kU/L, about 0.35 kU/L to about 100 kU/L, including values and rangestherebetween.

In yet another embodiment, a subject having a peanut allergy isdiagnosed as likely to respond favorably to the oral administration ofpeanut allergens if the subject has the peanut-specific serum IgE levelof about 0.35 kU/L to about 125 kU/L, about 0.35 kU/L to about 150 kU/L,about 0.35 kU/L to about 175 kU/L, about 0.35 kU/L to about 200 kU/L,about 0.35 kU/L to about 225 kU/L, about 0.35 kU/L to about 250 kU/L,about 0.35 kU/L to about 275 kU/L, about 0.35 kU/L to about 300 kU/L,about 0.35 kU/L to about 325 kU/L, about 0.35 kU/L to about 350 kU/L,about 0.35 kU/L to about 375 kU/L, about 0.35 kU/L to about 400 kU/L,about 0.35 kU/L to about 425 kU/L, or about 0.35 kU/L to about 450 kU/L,including values and ranges therebetween. In still another embodiment, asubject having a peanut allergy is diagnosed as likely to respondfavorably to the oral administration of peanut allergens if the subjecthas the peanut-specific serum IgE level of less than about 100 kU/L toabout 125 kU/L, less than about 100 kU/L to about 150 kU/L, less thanabout 100 kU/L to about 175 kU/L, less than about 100 kU/L to about 200kU/L, less than about 200 kU/L to about 250 kU/L, less than about 200kU/L to about 300 kU/L, less than about 300 kU/L to about 350 kU/L, orless than about 300 kU/L to about 400 kU/L, including values and rangestherebetween.

In one embodiment, a subject having a peanut allergy is diagnosed asunlikely to respond favorably to the oral administration of peanutallergens if the subject has the peanut-specific serum IgE level ofabout 50 kU/L or more, about 55 kU/L or more, about 60 kU/L or more,about 65 kU/L or more, about 70 kU/L or more, about 75 kU/L or more,about 80 kU/L or more, about 85 kU/L or more, about 90 kU/L or more,about 95 kU/L or more, about 100 kU/L or more, about 125 kU/L or more,about 150 kU/L or more, about 175 kU/L or more, about 200 kU/L or more,about 225 kU/L or more, about 250 kU/L or more, about 275 kU/L or more,about 300 kU/L or more, about 325 kU/L or more, about 350 kU/L or more,about 375 kU/L or more, or about 400 kU/L or more, including values andranges therebetween.

In some embodiments, the subject being treated is suffering from apeanut allergy and at least one dose of an allergen compositioncomprising peanut flour is administered to the subject orally.

Allergen compositions administered as OIT may comprise a food sourcecomprising one or one or more characterized allergen proteins andpharmaceutically acceptable excipients. For instance, in one embodiment,the allergen composition comprises one or more characterized peanutproteins and pharmaceutically acceptable excipients. In someembodiments, the amount of peanut proteins in the allergen compositionranges from about 0.05% to about 100% w/w.

Allergen compositions for treating peanut allergy may comprisecharacterized peanut proteins selected from the group consisting ofcharacterized Ara h1 proteins, characterized Ara h2 proteins,characterized Ara h6 proteins, and combinations thereof.

In some embodiments, allergen compositions for treating peanut allergycomprise one or more characterized Ara h1 proteins in an amount of fromabout 0.035 to about 65 mg. In some other embodiments, allergencompositions comprise one or more characterized Ara h2 proteins in anamount of from about 0.035 to about 60 mg. In yet some otherembodiments, allergen compositions comprise one or more characterizedAra h6 proteins in an amount of from about 0.015 to about 40 mg.

Methods of Identifying a Subject Suitable for Treatment

In some embodiments, a subject with a peanut allergy is identified assuitable for treatment or selected for treatment of a peanut allergybased on having a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L). Further, a subjectwith a peanut allergy can be identified as not suitable for treatment ornot selected for treatment of a peanut allergy based on having a levelof peanut-specific IgEs above the predetermined threshold. In someembodiments, the level of peanut-specific IgEs is a primary factor indetermining whether a subject is identified as suitable for treatment orselected for treatment of the peanut allergy. In some embodiments, thelevel of peanut-specific IgEs is an exclusive factor in determiningwhether the subject is identified as suitable for treatment or selectedfor treatment of the peanut allergy. In some embodiments, the subjectwith a peanut allergy is identified as suitable for treatment orselected for treatment only if the subject has a level ofpeanut-specific IgEs at or below a predetermined threshold (such asabout 100 kU/L). For example, in some embodiments, the subject with apeanut allergy is identified as suitable for treatment of the peanutallergy only if the subject has a level of peanut-specific IgEs at orbelow the predetermined threshold (such as about 100 kU/L). In someembodiments, the subject with a peanut allergy is selected for treatmentof the peanut allergy only if the subject has a level of peanut-specificIgE at or below the predetermined threshold (such as about 100 kU/L). Insome embodiments, the treatment is an oral immunotherapy dosing regimen.In some embodiments, the method further comprises receiving the level ofpeanut-specific IgEs, or measuring the level of peanut-specific IgEs.

In some embodiments, the level of peanut-specific IgEs is a level in thesubject prior to initiation of the treatment. In some embodiments, thelevel of peanut-specific IgEs is determined in the subject at a timeproximal to the selection or identification of the subject fortreatment, for example within about 7 days, within about 5 days, withinabout 72 hours, within about 48 hours, within about 24 hours, withinabout 12 hours, within about 6 hours, within about 4 hours, within about3 hours, within about 2 hours, or within about 1 hour of selecting thesubject for treatment or identifying the subject as suitable fortreatment. In some embodiments, the method includes receiving ormeasuring a level of peanut-specific IgEs in a subject prior toinitiation of the treatment, and selecting the subject for treatmentbased on having a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L).

In some embodiments, there is a method of identifying a subject with apeanut allergy suitable for treatment of the peanut allergy, comprisingevaluating a level of peanut-specific IgEs in the subject, wherein thesubject is identified as suitable for treatment based on having a levelof peanut-specific IgEs at or below a predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a primary factor in determining whether a subject is identified assuitable for treatment of the peanut allergy. In some embodiments, thelevel of peanut-specific IgEs is an exclusive factor in determiningwhether the subject is identified as suitable for treatment of thepeanut allergy. In some embodiments, the subject with a peanut allergyis identified as suitable for treatment only if the subject has a levelof peanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

In some embodiments, there is a method of selecting a subject with apeanut allergy for treatment of the peanut allergy, comprisingevaluating a level of peanut-specific IgEs in the subject, wherein thesubject is selected for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold. In someembodiments, the level of peanut-specific IgEs is a primary factor indetermining whether a subject is selected for treatment of the peanutallergy. In some embodiments, the level of peanut-specific IgEs is anexclusive factor in determining whether the subject is selected fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is selected for treatment only if the subject has a levelof peanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

In some embodiments, there is a method of identifying a subject with apeanut allergy suitable for treatment of the peanut allergy using anoral immunotherapy dosage regimen, comprising evaluating a level ofpeanut-specific IgEs in the subject, wherein the subject is identifiedas suitable for treatment using the oral immunotherapy dosing regimenbased on having a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a primary factor in determiningwhether a subject is identified as suitable for treatment of the peanutallergy. In some embodiments, the level of peanut-specific IgEs is anexclusive factor in determining whether the subject is identified assuitable for treatment of the peanut allergy. In some embodiments, thesubject with a peanut allergy is identified as suitable for treatmentonly if the subject has a level of peanut-specific IgEs at or below thepredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a level in the subject prior toinitiation of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined in the subject at a time proximal tothe identifying the subject for treatment.

In some embodiments, there is a method of selecting a subject with apeanut allergy for treatment of the peanut allergy using an oralimmunotherapy dosage regimen, comprising evaluating a level ofpeanut-specific IgEs in the subject, wherein the subject is selected fortreatment using the oral immunotherapy dosing regimen based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is selected for treatment of the peanut allergy. In someembodiments, the level of peanut-specific IgEs is an exclusive factor indetermining whether the subject is selected for treatment of the peanutallergy. In some embodiments, the subject with a peanut allergy isselected for treatment only if the subject has a level ofpeanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

In some embodiments, there is a method of identifying a subject with apeanut allergy suitable for treatment of the peanut allergy, comprising:receiving a level of peanut-specific IgEs in the subject; andidentifying the subject as suitable for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is identified as suitable for treatment of the peanut allergy.In some embodiments, the level of peanut-specific IgEs is an exclusivefactor in determining whether the subject is identified as suitable fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is identified as suitable for treatment only if thesubject has a level of peanut-specific IgEs at or below thepredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a level in the subject prior toinitiation of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined in the subject at a time proximal tothe identifying the subject for treatment.

In some embodiments, there is a method of selecting a subject with apeanut allergy for treatment of the peanut allergy, comprising:receiving a level of peanut-specific IgEs in the subject; and selectingthe subject for treatment based on having a level of peanut-specificIgEs at or below a predetermined threshold (such as about 100 kU/L). Insome embodiments, the level of peanut-specific IgEs is a primary factorin determining whether a subject is selected for treatment of the peanutallergy. In some embodiments, the level of peanut-specific IgEs is anexclusive factor in determining whether the subject is selected fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is selected for treatment only if the subject has a levelof peanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

In some embodiments, there is a method of identifying a subject with apeanut allergy as suitable for treatment of the peanut allergy using anoral immunotherapy dosage regimen, comprising: receiving a level ofpeanut-specific IgEs in the subject; and identifying the subject assuitable for treatment using the oral immunotherapy dosage regimen basedon having a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is identified as suitable for treatment of the peanut allergy.In some embodiments, the level of peanut-specific IgEs is an exclusivefactor in determining whether the subject is identified as suitable fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is identified as suitable for treatment only if thesubject has a level of peanut-specific IgEs at or below thepredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a level in the subject prior toinitiation of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined in the subject at a time proximal tothe identifying the subject for treatment.

In some embodiments, there is a method of selecting a subject with apeanut allergy for treatment of the peanut allergy using an oralimmunotherapy dosage regimen, comprising: receiving a level ofpeanut-specific IgEs in the subject; and selecting the subject fortreatment using the oral immunotherapy dosage regimen based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is selected for treatment of the peanut allergy. In someembodiments, the level of peanut-specific IgEs is an exclusive factor indetermining whether the subject is selected for treatment of the peanutallergy. In some embodiments, the subject with a peanut allergy isselected for treatment only if the subject has a level ofpeanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

In some embodiments, there is a method of identifying a subject with apeanut allergy suitable for treatment of the peanut allergy, comprising:measuring a level of peanut-specific IgEs in the subject; andidentifying the subject as suitable for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is identified as suitable for treatment of the peanut allergy.In some embodiments, the level of peanut-specific IgEs is an exclusivefactor in determining whether the subject is identified as suitable fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is identified as suitable for treatment only if thesubject has a level of peanut-specific IgEs at or below thepredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a level in the subject prior toinitiation of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined in the subject at a time proximal tothe identifying the subject for treatment.

In some embodiments, there is a method of selecting a subject with apeanut allergy for treatment of the peanut allergy, comprising:measuring a level of peanut-specific IgEs in the subject; and selectingthe subject for treatment based on having a level of peanut-specificIgEs at or below a predetermined threshold (such as about 100 kU/L). Insome embodiments, the level of peanut-specific IgEs is a primary factorin determining whether a subject is selected for treatment of the peanutallergy. In some embodiments, the level of peanut-specific IgEs is anexclusive factor in determining whether the subject is selected fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is selected for treatment only if the subject has a levelof peanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

In some embodiments, there is a method of identifying a subject with apeanut allergy as suitable for treatment of the peanut allergy using anoral immunotherapy dosage regimen, comprising: measuring a level ofpeanut-specific IgEs in the subject; and identifying the subject assuitable for treatment using the oral immunotherapy dosage regimen basedon having a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is identified as suitable for treatment of the peanut allergy.In some embodiments, the level of peanut-specific IgEs is an exclusivefactor in determining whether the subject is identified as suitable fortreatment of the peanut allergy. In some embodiments, the subject with apeanut allergy is identified as suitable for treatment only if thesubject has a level of peanut-specific IgEs at or below thepredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a level in the subject prior toinitiation of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined in the subject at a time proximal tothe identifying the subject for treatment.

In some embodiments, there is a method of selecting a subject with apeanut allergy for treatment of the peanut allergy using an oralimmunotherapy dosage regimen, comprising: measuring a level ofpeanut-specific IgEs in the subject; and selecting the subject fortreatment using the oral immunotherapy dosage regimen based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether asubject is selected for treatment of the peanut allergy. In someembodiments, the level of peanut-specific IgEs is an exclusive factor indetermining whether the subject is selected for treatment of the peanutallergy. In some embodiments, the subject with a peanut allergy isselected for treatment only if the subject has a level ofpeanut-specific IgEs at or below the predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of peanut-specific IgEsis a level in the subject prior to initiation of the treatment. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the identifying the subject for treatment.

Methods of Assessing Suitability of a Treatment for a Subject

The suitability of a treatment for a peanut allergy for a subject with apeanut allergy can be assessed in view of the level of peanut-specificIgEs in a subject. The level of peanut-specific IgE in the patient neednot be an exclusive factor in the suitability of treatment, but can be afactor taken into consideration when assessing the suitability of thetreatment for the subject. In some embodiments, a level ofpeanut-specific IgEs in the subject at or below a predeterminedthreshold (such as about 100 kU/L) indicates that the treatment issuitable for the subject. In some embodiments, the treatment is suitablefor the subject only if the level of peanut-specific IgEs in the subjectis at or below the predetermined threshold. In some embodiments, amethod of assessing the suitability of a treatment comprises receivingthe level of peanut-specific IgEs, or measuring the level ofpeanut-specific IgEs. In some embodiments, a level of peanut-specificIgEs in the subject above a predetermined threshold (such as about 100kU/L) indicates that the treatment is not suitable for the subject.

In some embodiments, the level of peanut-specific IgEs is a level in thesubject prior to initiation of the treatment or prior to the assessmentof the suitability of the treatment for the subject. In someembodiments, the level of peanut-specific IgEs is determined in thesubject at a time proximal to the assessment of the treatment for thesubject, for example within about 7 days, within about 5 days, withinabout 72 hours, within about 48 hours, within about 24 hours, withinabout 12 hours, within about 6 hours, within about 4 hours, within about3 hours, within about 2 hours, or within about 1 hour prior to assessingthe suitability of the treatment for the subject. In some embodiments,the method includes receiving or measuring a level of peanut-specificIgEs in a subject prior to assessing suitability of the treatment forthe subject.

In some embodiments, the treatment is an oral immunotherapy dosingregimen. In some embodiments, the treatment is a phase (or sub-phase) ofan oral immunotherapy dosing regimen, or other treatment. As furtherexplained herein, in some embodiments, a treatment regimen can includeone or more phases, such as an initial escalation phase (which maycomprise one or more sub-phase), an up-dosing phase (which may compriseone or more sub-phases), and/or a maintenance phase. In someembodiments, the suitability of the next phase or sub-phase of thetreatment regimen can be determined based on the level ofpeanut-specific IgEs in the subject. In some embodiments, the level ofpeanut-specific IgEs is received or measured following or prior to oneor more phases or sub-phases of the treatment regimen.

In some embodiments, a method of assessing the suitability of atreatment for a peanut allergy in a subject with a peanut allergycomprises: receiving a level of peanut-specific IgEs in the subject; andassessing the suitability of the treatment, wherein the subject having alevel of peanut specific IgEs at or below a predetermined threshold(such as about 100 kU/L) indicates that the treatment is suitable forthe subject. In some embodiments, the treatment is suitable for thesubject if the level of peanut-specific IgE is at or below thepredetermined threshold. In some embodiments, the treatment is a phase(such as an initial escalation phase, an up-dosing phase, or amaintenance phase) or a sub-phase (such as a dosage increase during aninitial escalation phase or a dosage increase during an up-dosing phase)of a treatment regimen. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to assessing thesuitability of the treatment for the subject.

In some embodiments, a method of assessing the suitability of an oralimmunotherapy dosing regimen for a peanut allergy in a subject with apeanut allergy comprises: receiving a level of peanut-specific IgEs inthe subject; and assessing the suitability of the oral immunotherapydosing regimen, wherein the subject having a level of peanut specificIgEs at or below a predetermined threshold (such as about 100 kU/L)indicates that the oral immunotherapy dosing regimen is suitable for thesubject. In some embodiments, the treatment is suitable for the subjectif the level of peanut-specific IgE is at or below the predeterminedthreshold. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to assessing the suitability of thetreatment for the subject.

In some embodiments, a method of assessing the suitability of a phase(such as an initial escalation phase, an up-dosing phase, or amaintenance phase) or sub-phase (such as a dosage increase during aninitial escalation phase or a dosage increase during an up-dosing phase)of an oral immunotherapy dosing regimen for treatment of a peanutallergy in a subject with a peanut allergy comprises: receiving a levelof peanut-specific IgEs in the subject prior to the phase or sub-phase;and assessing the suitability of the phase or sub-phase of the oralimmunotherapy dosing regimen, wherein the subject having a level ofpeanut specific IgEs at or below a predetermined threshold (such asabout 100 kU/L) indicates that the phase or sub-phase is suitable forthe subject. In some embodiments, the phase or sub-phase is suitable forthe subject if the level of peanut-specific IgE is at or below thepredetermined threshold. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to assessing thesuitability of the phase or sub-phase for the subject. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the start of the oral immunotherapy dosing regimen.

In some embodiments, a method of assessing the suitability of atreatment for a peanut allergy in a subject with a peanut allergycomprises: measuring a level of peanut-specific IgEs in the subject; andassessing the suitability of the treatment, wherein the subject having alevel of peanut specific IgEs at or below a predetermined threshold(such as about 100 kU/L) indicates that the treatment is suitable forthe subject. In some embodiments, the treatment is suitable for thesubject if the level of peanut-specific IgE is at or below thepredetermined threshold. In some embodiments, the treatment is a phase(such as an initial escalation phase, an up-dosing phase, or amaintenance phase) or a sub-phase (such as a dosage increase during aninitial escalation phase or a dosage increase during an up-dosing phase)of a treatment regimen. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to assessing thesuitability of the treatment for the subject.

In some embodiments, a method of assessing the suitability of an oralimmunotherapy dosing regimen for a peanut allergy in a subject with apeanut allergy comprises: measuring a level of peanut-specific IgEs inthe subject; and assessing the suitability of the oral immunotherapydosing regimen, wherein the subject having a level of peanut specificIgEs at or below a predetermined threshold (such as about 100 kU/L)indicates that the oral immunotherapy dosing regimen is suitable for thesubject. In some embodiments, the treatment is suitable for the subjectif the level of peanut-specific IgE is at or below the predeterminedthreshold. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to assessing the suitability of thetreatment for the subject.

In some embodiments, a method of assessing the suitability of a phase(such as an initial escalation phase, an up-dosing phase, or amaintenance phase) or sub-phase (such as a dosage increase during aninitial escalation phase or a dosage increase during an up-dosing phase)of an oral immunotherapy dosing regimen for treatment of a peanutallergy in a subject with a peanut allergy comprises: measuring a levelof peanut-specific IgEs in the subject prior to the phase or sub-phase;and assessing the suitability of the phase or sub-phase of the oralimmunotherapy dosing regimen, wherein the subject having a level ofpeanut specific IgEs at or below a predetermined threshold (such asabout 100 kU/L) indicates that the phase or sub-phase is suitable forthe subject. In some embodiments, the phase or sub-phase is suitable forthe subject if the level of peanut-specific IgE is at or below thepredetermined threshold. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to assessing thesuitability of the phase or sub-phase for the subject. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the start of the oral immunotherapy dosing regimen.

Methods of Treatment

A subject having a peanut allergy can be treated for the peanut allergyby administering a series of doses of an allergenic peanut compositionto the subject during the course of a therapy regimen. The therapy caninclude increasing the dose of the allergenic peanut composition over aperiod of time, thereby desensitizing the subject to peanut antigens.The therapy may be multi-phasic, for example by including two, three, ormore phases, such as an initial escalation phase, an up-dosing phase,and/or a maintenance phase. The phases, such as the initial escalationphase or the up-dosing phase can include one or more sub-phases, inwhich a dose of the allergenic peanut composition is periodicallyincreased. In some embodiments, the treatment therapy is an oralimmunotherapy dosing regimen.

The initial escalation phase can include administration of a pluralityof small doses of the allergenic peanut composition to the subject,which may occur in the same day. The small doses can be spaced by aperiod of time, such as about 10 minutes to about 60 minutes, or about20 minutes to about 30 minutes. The initial escalation phase may include1, 2, 3, 4, or 5 or more doses. The doses may be, for example betweenabout 0.1 mg peanut protein to about 6 mg peanut protein.

The up-dosing phase of an oral immunotherapy can be divided into aplurality of sub-phases. Treatment during the up-dosing phase caninclude administering to the subject a plurality of doses of anallergenic peanut composition, which are periodically increased. Forexample, each sub-phase can include administering a daily dose of theallergenic peanut composition for a period of time, such as two weeks.After the completion of the sub-phase, treatment can be advanced into asubsequent sub-phase in which an increased daily dose of the allergenicpeanut composition is administered for a period of time, such as abouttwo weeks. In some embodiments, the up-dosing phase of the treatmentcomprises between 2 sub-phases and 10 sub-phases. In some embodiments,the doses administered during the up-dosing phase range from about 3 mgpeanut protein to about 300 mg peanut protein.

Treatment of the peanut allergy can include a maintenance phase in whicha dose of the allergenic peanut composition is regularly administered tothe subject. The maintenance dose can be at the same dose or a higherdose as the dose administered during the final sub-phase of theup-dosing phase. The maintenance dose can be, for example, about 200 mgto about 500 mg peanut protein, such as about 250 mg to about 400 mg, orabout 300 mg peanut protein. In some embodiments, the maintenance doseis administered daily. In some embodiments, the maintenance dose isadministered for about 24 weeks.

The level of peanut-specific IgE in the subject can be a factor takeninto consideration when selecting how and/or whether the subject shouldbe treated during the course of treatment. For example, in someembodiments, the subject is selected for a treatment regimen based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the subject isselected for the treatment regimen only if the level of peanut-specificIgEs is at or below the predetermined threshold. A level ofpeanut-specific IgE above the predetermined threshold does notnecessarily exclude a subject from treatment. For example, in someembodiments, the subject undergoes heightened monitoring for an allergicreaction (such as a hypersensitivity, anaphylaxis (for exampleanaphylactic shock), gastrointestinal symptoms (such as abdominal painor vomiting), or eosinophilic esophagitis (EoE)). The level ofpeanut-specific IgE in the subject can also be taken into considerationas to whether the subject can be advanced to a subsequent phase orsub-phase of the treatment regimen.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising administering to the subject at least onedose of an allergenic peanut composition, wherein the subject isselected for treatment based on having a level of peanut-specific IgEsat or below a predetermined threshold (such as about 100 kU/L). In someembodiments, the level of peanut-specific IgEs is a primary factor indetermining whether the dose should be administered. In someembodiments, the level of peanut-specific IgEs is an exclusive factor indetermining whether the dose should be administered. In someembodiments, the dose is administered to the subject only if the levelof peanut-specific IgEs is at or below the predetermined threshold. Insome embodiments, the level of peanut-specific IgEs is determined priorto the initiation of treatment. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to the initiationof treatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprisingorally administering to the subject at least one dose of an allergenicpeanut composition, wherein the subject is selected for treatment basedon having a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprisingorally administering to the subject at least one dose of an allergenicpeanut composition during an initial escalation phase of the oralimmunotherapy dosing regimen, wherein the subject is selected fortreatment based on having a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L) at the start of theinitial escalation phase. In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of the initial escalation phase of thetreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprisingorally administering to the subject at least one dose of an allergenicpeanut composition during an up-dosing phase of the oral immunotherapydosing regimen, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of an initial escalation phase of thetreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined at a time proximal to the initiation of an up-dosing phase ofthe treatment. In some embodiments, the level of the peanut-specificIgEs is determined at a time proximal to the initiation of an up-dosingsub-phase of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to theadministration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprisingorally administering to the subject at least one dose of an allergenicpeanut composition during a maintenance phase of the oral immunotherapydosing regimen, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of an initial escalation phase of thetreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined at a time proximal to the initiation of an up-dosing phase ofthe treatment. In some embodiments, the level of the peanut-specificIgEs is determined at a time proximal to the initiation of an up-dosingsub-phase of the treatment. In some embodiments, the level of thepeanut-specific IgEs is determined at a time proximal to the initiationof a maintenance phase of the treatment. In some embodiments, the levelof peanut-specific IgEs is determined at a time proximal to theadministration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: receiving a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition, wherein the subject is selected fortreatment based on having a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a primary factor in determiningwhether the dose should be administered. In some embodiments, the levelof peanut-specific IgEs is an exclusive factor in determining whetherthe dose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:receiving a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:receiving a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition during an initial escalation phase of the oral immunotherapydosing regimen, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L) at the start of the initialescalation phase. In some embodiments, the level of peanut-specific IgEsis a primary factor in determining whether the dose should beadministered. In some embodiments, the level of peanut-specific IgEs isan exclusive factor in determining whether the dose should beadministered. In some embodiments, the dose is administered to thesubject only if the level of peanut-specific IgEs is at or below thepredetermined threshold. In some embodiments, the level ofpeanut-specific IgEs is determined prior to the initiation of treatment.In some embodiments, the level of peanut-specific IgEs is determined ata time proximal to the initiation of treatment. In some embodiments, thelevel of the peanut-specific IgEs is determined at a time proximal tothe initiation of the initial escalation phase of the treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:receiving a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition during an up-dosing phase of the oral immunotherapy dosingregimen, wherein the subject is selected for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of an initial escalation phase of thetreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined at a time proximal to the initiation of an up-dosing phase ofthe treatment. In some embodiments, the level of the peanut-specificIgEs is determined at a time proximal to the initiation of an up-dosingsub-phase of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to theadministration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:receiving a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition during a maintenance phase of the oral immunotherapy dosingregimen, wherein the subject is selected for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of an initial escalation phase of thetreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined at a time proximal to the initiation of an up-dosing phase ofthe treatment. In some embodiments, the level of the peanut-specificIgEs is determined at a time proximal to the initiation of an up-dosingsub-phase of the treatment. In some embodiments, the level of thepeanut-specific IgEs is determined at a time proximal to the initiationof a maintenance phase of the treatment. In some embodiments, the levelof peanut-specific IgEs is determined at a time proximal to theadministration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition, wherein the subject is selected fortreatment based on having a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L). In some embodiments,the level of peanut-specific IgEs is a primary factor in determiningwhether the dose should be administered. In some embodiments, the levelof peanut-specific IgEs is an exclusive factor in determining whetherthe dose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:measuring a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:measuring a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition during an initial escalation phase of the oral immunotherapydosing regimen, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold (such as about 100 kU/L) at the start of the initialescalation phase. In some embodiments, the level of peanut-specific IgEsis a primary factor in determining whether the dose should beadministered. In some embodiments, the level of peanut-specific IgEs isan exclusive factor in determining whether the dose should beadministered. In some embodiments, the dose is administered to thesubject only if the level of peanut-specific IgEs is at or below thepredetermined threshold. In some embodiments, the level ofpeanut-specific IgEs is determined prior to the initiation of treatment.In some embodiments, the level of peanut-specific IgEs is determined ata time proximal to the initiation of treatment. In some embodiments, thelevel of the peanut-specific IgEs is determined at a time proximal tothe initiation of the initial escalation phase of the treatment. In someembodiments, the level of peanut-specific IgEs is determined at a timeproximal to the administration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:measuring a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition during an up-dosing phase of the oral immunotherapy dosingregimen, wherein the subject is selected for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of an initial escalation phase of thetreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined at a time proximal to the initiation of an up-dosing phase ofthe treatment. In some embodiments, the level of the peanut-specificIgEs is determined at a time proximal to the initiation of an up-dosingsub-phase of the treatment. In some embodiments, the level ofpeanut-specific IgEs is determined at a time proximal to theadministration of the dose.

In some embodiments, there is a method of treating a subject for apeanut allergy using an oral immunotherapy dosing regimen, comprising:measuring a level of peanut-specific IgEs in the subject; and orallyadministering to the subject at least one dose of an allergenic peanutcomposition during a maintenance phase of the oral immunotherapy dosingregimen, wherein the subject is selected for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is a primary factor in determining whether the doseshould be administered. In some embodiments, the level ofpeanut-specific IgEs is an exclusive factor in determining whether thedose should be administered. In some embodiments, the dose isadministered to the subject only if the level of peanut-specific IgEs isat or below the predetermined threshold. In some embodiments, the levelof peanut-specific IgEs is determined prior to the initiation oftreatment. In some embodiments, the level of peanut-specific IgEs isdetermined at a time proximal to the initiation of treatment. In someembodiments, the level of the peanut-specific IgEs is determined at atime proximal to the initiation of an initial escalation phase of thetreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined at a time proximal to the initiation of an up-dosing phase ofthe treatment. In some embodiments, the level of the peanut-specificIgEs is determined at a time proximal to the initiation of an up-dosingsub-phase of the treatment. In some embodiments, the level of thepeanut-specific IgEs is determined at a time proximal to the initiationof a maintenance phase of the treatment. In some embodiments, the levelof peanut-specific IgEs is determined at a time proximal to theadministration of the dose.

Individuals allergic to peanut allergens and peanut allergeniccompositions risk an allergic response upon exposure to the allergeniccompounds. Although the level of peanut-specific IgEs determined priorto or during the course of treatment can be used to predict the risk ofan adverse event subjects may nevertheless suffer from an adverse eventduring the course of treatment. A severe or life threatening adverseevent related to peanut allergy is often treated by administeringinjectable epinephrine (adrenaline) to the subject. Under certaincircumstances, a single dose of epinephrine may not be sufficient, and asecond dose is administered to the subject to treat the allergicresponse. Doses are generally about 0.15 mg of injectable epinephrinefor subjects less than about 30 kilograms, or about 0.3 mg of injectableepinephrine if the subject weighs about 30 kilograms or more.

The level of IgEs in a subject receiving treatment (for example, an oralimmunotherapy dosing regimen) for a peanut allergy by administering atleast one dose of an allergic peanut composition to the subject can beused to assess the likelihood of an allergic reaction that requiresadministration of epinephrine to the subject. The method includesreceiving a level of peanut-specific IgEs in the subject (which may bedetermined prior to or during the course of treatment); and assessingthe likelihood of an allergic reaction that requires administration ofepinephrine to the patient, wherein a level of peanut-specific IgEs ator below a predetermined threshold indicates a reduced likelihood of anallergic reaction that requires administration of epinephrine duringtreatment, and wherein a level of peanut-specific IgEs above thepredetermined threshold indicates an increased likelihood of an allergicreaction that requires administration of epinephrine during treatment.The predetermined threshold of the level of peanut-specific IgEs may be,for example, about 100 kU/L. The method can also include administeringto the subject at least one dose of an allergic peanut composition. Insome embodiments, the method includes measuring the level ofpeanut-specific of IgEs. If the subject has a level of peanut-specificIgEs above the predetermined threshold, and therefore has an increasedlikelihood of an allergic reaction that requires administering ofepinephrine during treatment, the subject is not precluded from beingtreated. However, it may be recommended or prescribed to the subjectthat the subject have immediate access to at least two doses ofepinephrine if the subject has a level of peanut-specific IgEs above thepredetermined threshold. The epinephrine is generally injected in thepatient for treatment of the allergic reaction by subcutaneousinjection.

In some embodiments, the subjects treated for the peanut allergy, forexample by oral immunotherapy are 18 years of age or older. In someembodiments, the subjects treated for the peanut allergy are 17 years ofage or younger (such as between about 4 years of age and about 17 yearsof age, between about 4 years of age and 11 years of age, or betweenabout 12 years of age and about 17 years of age).

Methods of Monitoring a Subject for an Adverse Event

As mentioned above, a level of peanut-specific IgEs in a subject abovethe predetermined threshold does not necessarily exclude the subjectfrom treatment of a peanut allergy. However, in some embodiments, asubject having a level of peanut-specific IgEs above the predeterminedthreshold (such as about 100 kU/L) indicates that the subject is in needof heightened monitoring for an allergic reaction during the course ofthe immunotherapy or following administration of a dose of theallergenic peanut composition. Such heightened monitoring may include,for example, active monitoring of the subject for symptoms of anallergic reaction (such as hypersensitivity, anaphylaxis,gastrointestinal symptoms, or eosinophilic esophagitis) in a clinicalsetting after administration of the dose of the allergenic peanutcomposition, which may be longer monitoring period than for a subjectwith a level of peanut-specific IgEs below the predetermined threshold;an increased frequency of clinical visits after beginning an up-dosingsub-phase; monitoring of heart rate and/or respiratory rate of thesubject for a period of time after administration of the dose of theallergenic peanut composition; monitoring blood oxygen of the subjectfor a period of time after administration of the dose of the allergenicpeanut composition; or monitoring of blood pressure of the subject for aperiod of time after administration of the dose of the allergenic peanutcomposition.

During the course of treatment, such as by oral immunotherapy, the levelof peanut-specific IgEs can increase before decreasing. For example, thelevel of peanut-specific IgEs in a subject at the end of an up-dosingphase may be substantially higher (such as above a predeterminedthreshold such as about 100 kU/L) than the level of peanut-specific IgEsin the subject prior to the start of treatment. However, it has beenfound that the level of peanut-specific IgEs decreases during themaintenance phase of treatment. Since a level of peanut-specific IgEsabove a predetermined threshold (such as about 100 kU/L) indicates aneed for heightened monitoring and a level of peanut-specific IgEs belowthe predetermined threshold can indicate a decreased need (compared to asubject with a level of peanut-specific IgEs above the predeterminedthreshold) or no need for heightened monitoring, monitoring of the levelof peanut-specific IgEs can be a useful indicator for monitoring thesubject during the course of treatment. For example, monitoring thesubject for an adverse event can include measuring a level ofpeanut-specific IgEs in the subject during the course of treatment, suchas during an up-dosing phase of treatment or a maintenance phase oftreatment, wherein a level of peanut-specific IgEs above a predeterminedthreshold (such as about 100 kU/L) indicates a need for heightenedmonitoring, a delayed or skipped dose of the allergenic peanutcomposition, or a decreased dose of the allergenic peanut composition.

By way of example, a level of peanut-specific IgEs are monitored insubject during a maintenance phase of a treatment for a peanut allergy,such as an oral immunotherapy treatment regimen. The peanut-specific IgElevel can be measured, for example, weekly, every two weeks, or monthlyduring the maintenance phase. During the maintenance phase of thetreatment phase, the level of peanut-specific IgEs decreases. If thesubject has a level of peanut-specific IgEs below the predeterminedthreshold (such as about 100 kU/L), heightened monitoring is not neededand can be suspended if previously employed. If the subject has a levelof peanut-specific IgEs above the predetermined threshold (such as about100 kU/L), the subject can be subjected to heightened monitoring adelayed or skipped dose of the allergenic peanut composition, or adecreased dose of the allergenic peanut composition until the level ofpeanut-specific IgEs is below the predetermined threshold.

The level of peanut-specific IgEs may be determined in the subject at atime proximal to the start of treatment, a time proximal to theadministration of the dose, or at a time proximal to the start of aphase or sub-phase of a treatment regimen. For example, in someembodiments, the level of peanut-specific IgEs is determinedapproximately within 7 days, within 5 days, within 72 hours, within 48hours, within 24 hours, within 12 hours, within 6 hours, within 4 hours,within 3 hours, within 2 hours, or within 1 hour prior to the initiationof the treatment, the administration of the dose, or initiation of aphase or sub-phase of the treatment regimen.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising administering to the subject at least onedose of an allergenic peanut composition, wherein the subject undergoesheightened monitoring for an allergic reaction if a level ofpeanut-specific IgEs in the subject is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of treatment. Insome embodiments, the level of peanut-specific IgEs is determinedproximal to administration of the dose. In some embodiments, heightenedmonitoring comprises a longer clinical visit following administration ofthe dose compared to a subject having a level of peanut-specific IgEs ator below the predetermined threshold. In some embodiments, heightenedmonitoring comprises active monitoring of one or more symptoms relatedto an allergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising administering to the subject at least onedose of an allergenic peanut composition as part of an oralimmunotherapy dosing regimen, wherein the subject undergoes heightenedmonitoring for an allergic reaction if a level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to administrationof the dose. In some embodiments, heightened monitoring comprises alonger clinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising administering to the subject at least onedose of an allergenic peanut composition as part of an initialescalation phase of an oral immunotherapy dosing regimen, wherein thesubject undergoes heightened monitoring for an allergic reaction if alevel of peanut-specific IgEs in the subject is above a predeterminedthreshold (such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of the oralimmunotherapy dosing regimen. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose. In some embodiments, heightened monitoring comprises a longerclinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising administering to the subject at least onedose of an allergenic peanut composition as part of an up-dosing phaseof an oral immunotherapy dosing regimen, wherein the subject undergoesheightened monitoring for an allergic reaction if a level ofpeanut-specific IgEs in the subject is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of the oralimmunotherapy dosing regimen. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to the start of theup-dosing phase of the oral immunotherapy dosing regimen. In someembodiments, the level of peanut-specific IgEs is determined proximal toadministration of the dose. In some embodiments, heightened monitoringcomprises a longer clinical visit following administration of the dosecompared to a subject having a level of peanut-specific IgEs at or belowthe predetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising administering to the subject at least onedose of an allergenic peanut composition as part of a maintenance phaseof an oral immunotherapy dosing regimen, wherein the subject undergoesheightened monitoring for an allergic reaction if a level ofpeanut-specific IgEs in the subject is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of treatment. Insome embodiments, the level of peanut-specific IgEs is determinedproximal to the start of the maintenance phase of the oral immunotherapydosing regimen. In some embodiments, the level of peanut-specific IgEsis determined proximal to administration of the dose. In someembodiments, heightened monitoring comprises a longer clinical visitfollowing administration of the dose compared to a subject having alevel of peanut-specific IgEs at or below the predetermined threshold.In some embodiments, heightened monitoring comprises active monitoringof one or more symptoms related to an allergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: receiving a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to administrationof the dose. In some embodiments, heightened monitoring comprises alonger clinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: receiving a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of an oral immunotherapy dosingregimen, wherein the subject undergoes heightened monitoring for anallergic reaction if the level of peanut-specific IgEs in the subject isabove a predetermined threshold (such as about 100 kU/L). In someembodiments, the level of peanut-specific IgEs is determined prior tothe start of treatment. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose. In some embodiments, heightened monitoring comprises a longerclinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: receiving a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of an initial escalation phase ofan oral immunotherapy dosing regimen, wherein the subject undergoesheightened monitoring for an allergic reaction if the level ofpeanut-specific IgEs in the subject is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of the oralimmunotherapy dosing regimen. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose. In some embodiments, heightened monitoring comprises a longerclinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: receiving a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of an up-dosing phase of an oralimmunotherapy dosing regimen, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of the oral immunotherapy dosing regimen.In some embodiments, the level of peanut-specific IgEs is determinedproximal to the start of the up-dosing phase of the oral immunotherapydosing regimen. In some embodiments, the level of peanut-specific IgEsis determined proximal to administration of the dose. In someembodiments, heightened monitoring comprises a longer clinical visitfollowing administration of the dose compared to a subject having alevel of peanut-specific IgEs at or below the predetermined threshold.In some embodiments, heightened monitoring comprises active monitoringof one or more symptoms related to an allergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: receiving a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of a maintenance phase of an oralimmunotherapy dosing regimen, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to the start of themaintenance phase of the oral immunotherapy dosing regimen. In someembodiments, the level of peanut-specific IgEs is determined proximal toadministration of the dose. In some embodiments, heightened monitoringcomprises a longer clinical visit following administration of the dosecompared to a subject having a level of peanut-specific IgEs at or belowthe predetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to administrationof the dose. In some embodiments, heightened monitoring comprises alonger clinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of an oral immunotherapy dosingregimen, wherein the subject undergoes heightened monitoring for anallergic reaction if the level of peanut-specific IgEs in the subject isabove a predetermined threshold (such as about 100 kU/L). In someembodiments, the level of peanut-specific IgEs is determined prior tothe start of treatment. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of an initial escalation phase ofan oral immunotherapy dosing regimen, wherein the subject undergoesheightened monitoring for an allergic reaction if the level ofpeanut-specific IgEs in the subject is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of the oralimmunotherapy dosing regimen. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose. In some embodiments, heightened monitoring comprises a longerclinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of an up-dosing phase of an oralimmunotherapy dosing regimen, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of the oral immunotherapy dosing regimen.In some embodiments, the level of peanut-specific IgEs is determinedproximal to the start of the up-dosing phase of the oral immunotherapydosing regimen. In some embodiments, the level of peanut-specific IgEsis determined proximal to administration of the dose. In someembodiments, heightened monitoring comprises a longer clinical visitfollowing administration of the dose compared to a subject having alevel of peanut-specific IgEs at or below the predetermined threshold.In some embodiments, heightened monitoring comprises active monitoringof one or more symptoms related to an allergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition as part of a maintenance phase of an oralimmunotherapy dosing regimen, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to the start of themaintenance phase of the oral immunotherapy dosing regimen. In someembodiments, the level of peanut-specific IgEs is determined proximal toadministration of the dose. In some embodiments, heightened monitoringcomprises a longer clinical visit following administration of the dosecompared to a subject having a level of peanut-specific IgEs at or belowthe predetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; and administering to the subject at least one dose of anallergenic peanut composition, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the level of peanut-specific IgEsin the subject is above a predetermined threshold (such as about 100kU/L). In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to administrationof the dose. In some embodiments, heightened monitoring comprises alonger clinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; administering to the subject at least one dose of anallergenic peanut composition as part of an oral immunotherapy dosingregimen; and monitoring the subject, wherein the subject undergoesheightened monitoring for an allergic reaction if the level ofpeanut-specific IgEs in the subject is above a predetermined threshold(such as about 100 kU/L) compared to a subject that has a level ofpeanut-specific IgE at or less than the predetermined threshold. In someembodiments, the level of peanut-specific IgEs is determined prior tothe start of treatment. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose. In some embodiments, heightened monitoring comprises a longerclinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; administering to the subject at least one dose of anallergenic peanut composition as part of an initial escalation phase ofan oral immunotherapy dosing regimen; and monitoring the subject,wherein the subject undergoes heightened monitoring for an allergicreaction if the level of peanut-specific IgEs in the subject is above apredetermined threshold (such as about 100 kU/L) compared to a subjectthat has a level of peanut-specific IgE at or less than thepredetermined threshold. In some embodiments, the level ofpeanut-specific IgEs is determined prior to the start of the oralimmunotherapy dosing regimen. In some embodiments, the level ofpeanut-specific IgEs is determined proximal to administration of thedose. In some embodiments, heightened monitoring comprises a longerclinical visit following administration of the dose compared to asubject having a level of peanut-specific IgEs at or below thepredetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; administering to the subject at least one dose of anallergenic peanut composition as part of an up-dosing phase of an oralimmunotherapy dosing regimen; and monitoring the subject, wherein thesubject undergoes heightened monitoring for an allergic reaction if thelevel of peanut-specific IgEs in the subject is above a predeterminedthreshold (such as about 100 kU/L) compared to a subject that has alevel of peanut-specific IgE at or less than the predeterminedthreshold. In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of the oral immunotherapy dosing regimen.In some embodiments, the level of peanut-specific IgEs is determinedproximal to the start of the up-dosing phase of the oral immunotherapydosing regimen. In some embodiments, the level of peanut-specific IgEsis determined proximal to administration of the dose. In someembodiments, heightened monitoring comprises a longer clinical visitfollowing administration of the dose compared to a subject having alevel of peanut-specific IgEs at or below the predetermined threshold.In some embodiments, heightened monitoring comprises active monitoringof one or more symptoms related to an allergic reaction.

In some embodiments, there is a method of treating a subject for apeanut allergy, comprising: measuring a level of peanut-specific IgEs inthe subject; administering to the subject at least one dose of anallergenic peanut composition as part of a maintenance phase of an oralimmunotherapy dosing regimen; and monitoring the subject, wherein thesubject undergoes heightened monitoring for an allergic reaction if thelevel of peanut-specific IgEs in the subject is above a predeterminedthreshold (such as about 100 kU/L) compared to a subject that has alevel of peanut-specific IgE at or less than the predeterminedthreshold. In some embodiments, the level of peanut-specific IgEs isdetermined prior to the start of treatment. In some embodiments, thelevel of peanut-specific IgEs is determined proximal to the start of themaintenance phase of the oral immunotherapy dosing regimen. In someembodiments, the level of peanut-specific IgEs is determined proximal toadministration of the dose. In some embodiments, heightened monitoringcomprises a longer clinical visit following administration of the dosecompared to a subject having a level of peanut-specific IgEs at or belowthe predetermined threshold. In some embodiments, heightened monitoringcomprises active monitoring of one or more symptoms related to anallergic reaction.

Ongoing Monitoring During the Course of Treatment

In some embodiments, biomarkers described herein, such a level ofpeanut-specific IgE, antigen-specific IgE (such as Ara h1, Ara h2,and/or Ara h6 specific IgE), peanut-specific IgG4, antigen-specific IgG4(such as Ara h1, Ara h2, and/or Ara h6 specific IgG4), the ratio ofpeanut-specific IgE to peanut-specific IgG4 (“psIgE/psIgG4”), or theratio of antigen-specific IgE to antigen-specific IgG4 in the subjectcan be monitored during the course of treatment of the peanut allergy,such as an oral immunotherapy dosing regimen. The level of the biomarkercan be measured one or more (such as 2, 3, 4, 5, 6, 7, 8, 9, or 10 ormore) times during the course of treatment. In some embodiments, thelevel of the biomarker in the subject is measured during or after aninitial escalation phase of the treatment, before, during, or after anup-dosing phase or up-dosing sub-phase of the treatment, or before orduring a maintenance phase of the treatment.

The level of peanut-specific IgEs in the subject can also be useful formonitoring the subject during the course of treatment of the peanutallergy, for example during the course of an oral immunotherapy dosingregimen. The level of peanut-specific IgEs can be used, for example, tohelp reduce the risk or incidence of an adverse event in a subjectreceiving treatment for the peanut allergy, to evaluate a symptom thatmay arise during the course of treatment of the peanut allergy, or toadjust a dose or dosing schedule of administration of an allergenicpeanut composition.

The level of peanut-specific IgEs in the subject is also associated witha likelihood of an allergic reaction (such as a hypersensitivity,anaphylaxis (for example anaphylactic shock), gastrointestinal symptoms(such as abdominal pain or vomiting), or eosinophilic esophagitis(EoE)). Therefore, a reduction of the level of peanut-specific IgEsduring the course of treatment indicates the patient is less likely tohave an allergic reaction, and the level of peanut-specific IgEs can bemeasured to monitor this likelihood. The reduction of the level ofpeanut-specific IgEs can be measured for example, at two or more timepoints during the course of treatment. In some embodiments, the level ofpeanut-specific IgE is measured at the start of maintenance phase oftreatment and during the maintenance phase of treatment.

A subject that has a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L) has a low risk of anadverse event related to treatment of the peanut allergy compared to asubject having a level of peanut-specific IgEs above the predeterminedthreshold. The risk of an adverse event in a subject being related tothe treatment regimen (such as an oral immunotherapy dosing regimen) issufficiently small that the level of peanut-specific IgEs in the subjectcan be used as a factor taken into consideration when determiningwhether the symptom is related to the treatment regimen. The symptomcould be a symptom of an allergic reaction, but could also be a symptomof another cause. For example, a gastrointestinal symptom, such asvomiting or abdominal pain, could be caused by an allergic reaction tothe dose of allergenic peanut composition administered during the courseof treatment, or could be caused by another source, such as agastrointestinal virus. The level of peanut-specific IgEs in the subjectcan be used as a factor in determining the source of the symptoms. Insome embodiments, the level of peanut-specific IgEs is determined at atime proximal to and/or prior to the start of the treatment regimen. Insome embodiments, the level of peanut-specific IgE is a level at orproximal to the initiation of treatment, and in some embodiments thelevel of peanut-specific IgE is a level during or proximal to thesymptom adverse event. In some embodiments, the level of peanut-specificIgEs is determined approximately within 7 days, within 5 days, within 72hours, within 48 hours, within 24 hours, within 12 hours, within 6hours, within 4 hours, within 3 hours, within 2 hours, or within 1 hourprior to the start of the treatment regimen. In some embodiments, thelevel of peanut-specific IgEs is determined during or proximal to thesymptom or adverse event.

If the symptom is determined to be related to the treatment for thepeanut allergy, or if the level of IgE in the subject is above thepredetermined threshold, the treatment, such as the amount of the doseor the dosing schedule, can be adjusted or terminated. For example, insome embodiments, administration of a dose is delayed or skipped if thesymptom is determined to be related to the treatment or if the level ofIgE in the subject is above the predetermined threshold. In someembodiments, a dose increase is delayed during an up-dosing phase of thetreatment if the symptom is determined to be related to the treatment orif the level of IgE in the subject is above the predetermined threshold.A delay may include, for example, a temporary pause in administration ofa dose for a period of time, such as about 60 days or less, about 45days or less, about 30 days or less, about 15 days or less. In someembodiments, a delay includes a temporary pause in administration of thedose for a period of time of about 10 days or more, about 15 days ormore, about 30 days or more, or about 45 days or more. In someembodiment, treatment is terminated if it is determined that the symptomis related to the treatment.

The level of peanut-specific IgEs in a subject can be used to monitortreatment for a peanut allergy in a subject. In some embodiments, amethod of monitoring treatment for a peanut allergy in a subjectcomprises measuring a level of peanut-specific IgEs in the subjectduring the course of treatment for the peanut allergy. In someembodiments, a method of monitoring treatment for a peanut allergy in asubject using an oral immunotherapy treatment regimen comprisesmeasuring a level of peanut-specific IgEs in the subject during thecourse of treatment. In some embodiments, the level of peanut-specificIgEs in the subject is measured during or after an initial escalationphase of the treatment, before, during, or after an up-dosing phase orup-dosing sub-phase of the treatment, or before or during a maintenancephase of the treatment. In some embodiments, the method includesadjusting a dose of an allergenic peanut composition based on the levelof peanut-specific IgEs in the subject. For example, in someembodiments, the dose is reduced (for example, during an up-dosing phaseor a maintenance phase of a treatment regimen) if the level ofpeanut-specific IgEs in the subject is above a pre-determined threshold(such as about 100 kU/L). In some embodiments, the dose is not increasedor an increase of the dose is delayed during an initial escalation phaseor an up-dosing phase of a treatment regimen if the level ofpeanut-specific IgEs in the subject is above the pre-determinedthreshold (such as about 100 kU/L). In some embodiments, the dose of theallergenic peanut composition is increased if or only if the level ofpeanut-specific IgEs in the subject is at or below the pre-determinedthreshold (such as about 100 kU/L).

In some embodiments, there is a method of evaluating a symptom in ansubject during the course of treatment of a peanut allergy, comprising:receiving a level of peanut-specific IgEs in the subject having asymptom; and determining whether the symptom is related to thetreatment, wherein a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L) indicates that thesymptom is not caused by the treatment. In some embodiments, the symptomis a gastrointestinal symptom, such as vomiting or abdominal pain. Insome embodiments, administration of a dose is delayed or skipped if thesymptom is determined to be related to the treatment. In someembodiments, a dose increase is delayed during an up-dosing phase of thetreatment if the symptom is determined to be related to the treatment.In some embodiment, treatment is terminated if it is determined that thesymptom is related to the treatment.

In some embodiments, there is a method of evaluating a symptom in ansubject during the course of treatment of a peanut allergy using an oralimmunotherapy dosing regimen, comprising: receiving a level ofpeanut-specific IgEs in the subject having a symptom; and determiningwhether the symptom is related to the treatment, wherein a level ofpeanut-specific IgEs at or below a predetermined threshold (such asabout 100 kU/L) indicates that the symptom is not caused by the oralimmunotherapy dosing regimen. In some embodiments, the symptom is agastrointestinal symptom, such as vomiting or abdominal pain.

In some embodiments, there is a method of evaluating a symptom in ansubject during the course of treatment of a peanut allergy, comprising:measuring a level of peanut-specific IgEs in the subject having asymptom; and determining whether the symptom is related to thetreatment, wherein a level of peanut-specific IgEs at or below apredetermined threshold (such as about 100 kU/L) indicates that thesymptom is not caused by the treatment. In some embodiments, the symptomis a gastrointestinal symptom, such as vomiting or abdominal pain. Insome embodiments, administration of a dose is delayed or skipped if thesymptom is determined to be related to the treatment. In someembodiments, a dose increase is delayed during an up-dosing phase of thetreatment if the symptom is determined to be related to the treatment.In some embodiment, treatment is terminated if it is determined that thesymptom is related to the treatment.

In some embodiments, there is a method of evaluating a symptom in ansubject during the course of treatment of a peanut allergy using an oralimmunotherapy dosing regimen, comprising: measuring a level ofpeanut-specific IgEs in the subject having a symptom; and determiningwhether the symptom is related to the treatment, wherein a level ofpeanut-specific IgEs at or below a predetermined threshold (such asabout 100 kU/L) indicates that the symptom is not caused by the oralimmunotherapy dosing regimen. In some embodiments, the symptom is agastrointestinal symptom, such as vomiting or abdominal pain. In someembodiments, administration of a dose is delayed or skipped if thesymptom is determined to be related to the treatment. In someembodiments, a dose increase is delayed during an up-dosing phase of thetreatment if the symptom is determined to be related to the treatment.In some embodiment, treatment is terminated if it is determined that thesymptom is related to the treatment.

As the risk or incidence of an adverse event in a subject receivingtreatment for a peanut allergy is associated with the level ofpeanut-specific IgEs in the subject, the risk or incidence of an adverseevent can be reduced by reducing a dose, delaying administration of adose, or not increasing a dose during treatment. In some embodiments,the level of peanut-specific IgEs is determined proximal to the time ofreducing, delaying, or not increasing the dose, such as about within 72hours prior, within 48 hours prior, within 24 hours prior, within 12hours prior, within 6 hours prior, within 4 hours prior, within 3 hoursprior, within 2 hours prior, or within 1 hour prior to reducing,delaying, or not increasing the dose. Generally, the dose is reduced,the dose is delayed, or the increase of the dose is delayed only if thesubject experiences a compounding factor in addition to a level ofpeanut-specific IgEs above the predetermined threshold. Such acompounding factor can include, for example, inflammation (which may besystemic inflammation or localized inflammation, for example due to alocalized injury or surgery), an infection (for example, a viral,fungal, parasitic, or bacterial infection), an allergic reaction (whichmay be due to peanut or other allergy causing agent), or a menstruationperiod. Both the compounding factor and the level of peanut-specificIgEs can be taken into consideration when deciding whether to delay thedose, decrease the dose, or delay increasing a dose of the peanutcomposition.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving treatment for a peanut allergycomprises: receiving a level of peanut-specific IgEs in the subject; andreducing or delaying a dose of an allergenic peanut composition if thelevel of the peanut-specific IgEs is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the level of thepeanut-specific IgEs is determined during the course of treatment. Insome embodiments, the level of the peanut-specific IgEs is determined inresponse to a symptom of an allergic reaction. In some embodiments, thedose is reduced or delayed during an up-dosing phase of the treatment.In some embodiments, the adverse event is an allergic reaction, such asanaphylaxis, a gastrointestinal symptom (such as vomiting or abdominalpain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving treatment for a peanut allergycomprises: receiving a level of peanut-specific IgEs in the subject; anddelaying increasing a dose of an allergenic peanut composition during anup-dosing phase of the treatment if the level of the peanut-specificIgEs is above a predetermined threshold (such as about 100 kU/L). Insome embodiments, the level of the peanut-specific IgEs is determinedduring the course of treatment. In some embodiments, the level of thepeanut-specific IgEs is determined in response to a symptom of anallergic reaction. In some embodiments, the adverse event is an allergicreaction, such as anaphylaxis, a gastrointestinal symptom (such asvomiting or abdominal pain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving oral immunotherapy for a peanutallergy comprises: receiving a level of peanut-specific IgEs in thesubject; and reducing or delaying a dose of an allergenic peanutcomposition if the level of the peanut-specific IgEs is above apredetermined threshold (such as about 100 kU/L). In some embodiments,the level of the peanut-specific IgEs is determined during the course oftreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined in response to a symptom of an allergic reaction. In someembodiments, the dose is reduced or delayed during an up-dosing phase ofthe treatment. In some embodiments, the adverse event is an allergicreaction, such as anaphylaxis, a gastrointestinal symptom (such asvomiting or abdominal pain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving oral immunotherapy for a peanutallergy comprises: receiving a level of peanut-specific IgEs in thesubject; and delaying increasing a dose of an allergenic peanutcomposition during an up-dosing phase of the treatment if the level ofthe peanut-specific IgEs is above a predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of the peanut-specificIgEs is determined during the course of treatment. In some embodiments,the level of the peanut-specific IgEs is determined in response to asymptom of an allergic reaction. In some embodiments, the adverse eventis an allergic reaction, such as anaphylaxis, a gastrointestinal symptom(such as vomiting or abdominal pain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving treatment for a peanut allergycomprises: measuring a level of peanut-specific IgEs in the subject; andreducing or delaying a dose of an allergenic peanut composition if thelevel of the peanut-specific IgEs is above a predetermined threshold(such as about 100 kU/L). In some embodiments, the dose is reducedduring an up-dosing phase of the treatment. In some embodiments, theadverse event is an allergic reaction, such as anaphylaxis oreosinophilic esophagitis. In some embodiments, the level of thepeanut-specific IgEs is determined during the course of treatment. Insome embodiments, the level of the peanut-specific IgEs is determined inresponse to a symptom of an allergic reaction. In some embodiments, thedose is reduced or delayed during an up-dosing phase of the treatment.In some embodiments, the adverse event is an allergic reaction, such asanaphylaxis, a gastrointestinal symptom (such as vomiting or abdominalpain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving treatment for a peanut allergycomprises: measuring a level of peanut-specific IgEs in the subject; anddelaying increasing a dose of an allergenic peanut composition during anup-dosing phase of the treatment if the level of the peanut-specificIgEs is above a predetermined threshold (such as about 100 kU/L). Insome embodiments, the level of the peanut-specific IgEs is determinedduring the course of treatment. In some embodiments, the level of thepeanut-specific IgEs is determined in response to a symptom of anallergic reaction. In some embodiments, the adverse event is an allergicreaction, such as anaphylaxis, a gastrointestinal symptom (such asvomiting or abdominal pain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving oral immunotherapy for a peanutallergy comprises: measuring a level of peanut-specific IgEs in thesubject; and reducing or delaying a dose of an allergenic peanutcomposition if the level of the peanut-specific IgEs is above apredetermined threshold (such as about 100 kU/L). In some embodiments,the dose is reduced during an up-dosing phase of the treatment. In someembodiments, the adverse event is an allergic reaction, such asanaphylaxis or eosinophilic esophagitis. In some embodiments, the levelof the peanut-specific IgEs is determined during the course oftreatment. In some embodiments, the level of the peanut-specific IgEs isdetermined in response to a symptom of an allergic reaction. In someembodiments, the dose is reduced or delayed during an up-dosing phase ofthe treatment. In some embodiments, the adverse event is an allergicreaction, such as anaphylaxis, a gastrointestinal symptom (such asvomiting or abdominal pain), or eosinophilic esophagitis.

In some embodiments, a method of reducing the risk or incidence of anadverse event in a subject receiving oral immunotherapy for a peanutallergy comprises: measuring a level of peanut-specific IgEs in thesubject; and delaying increasing a dose of an allergenic peanutcomposition during an up-dosing phase of the treatment if the level ofthe peanut-specific IgEs is above a predetermined threshold (such asabout 100 kU/L). In some embodiments, the level of the peanut-specificIgEs is determined during the course of treatment. In some embodiments,the level of the peanut-specific IgEs is determined in response to asymptom of an allergic reaction. In some embodiments, the adverse eventis an allergic reaction, such as anaphylaxis, a gastrointestinal symptom(such as vomiting or abdominal pain), or eosinophilic esophagitis.

During the course of treatment, a later dose or dosing schedule can beadjusted based on a previous dose and a level of peanut-specific IgEdetermined in response to the administration of the earlier dose. Insome embodiments, there method of adjusting a dose of an allergenicpeanut composition, comprising: administering a first dose of theallergenic peanut composition to a subject with a peanut allergy;receiving a level of peanut-specific IgEs in the subject afteradministration of the first dose; and administering a second dose of theallergenic peanut composition to the subject, wherein the second dose isbased on the first dose and the level of peanut-specific IgEs in thesubject. In some embodiments, the second dose is lower than the firstdose if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the administration of the second dose isdelayed if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the second dose is the same as the firstdose if the level of peanut-specific IgEs is above a predeterminedthreshold. In some embodiments, the second dose is increased relative tothe first dose if the level of peanut-specific IgEs is at or below thepredetermined threshold. In some embodiments, the predeterminedthreshold is about 100 kU/L. In some embodiments, receiving the level ofpeanut-specific IgEs in the subject comprises measuring the level ofpeanut-specific IgEs.

The level of peanut-specific IgG4 can additionally or alternatively bedetermined prior to treatment, determined or monitored during the courseof treatment, or determined at the end of treatment. For example, thelevel of peanut-specific IgG4 can be determined during or following anup-dosing phase and/or during or following a maintenance phase of thetreatment. During the course of treatment, the level of peanut-specificIgG4 generally increases, and an increase in the level ofpeanut-specific IgG4 is an indicator of successful oral immunotherapytreatment. Therefore, the level of peanut-specific IgG4 can be used tomonitor treatment of the peanut allergy. The level of peanut-specificIgG4 may be a total level of one or more (or all) of peanut allergenspecific IgG4. For example, the level of peanut-specific IgG4 may be alevel of Ara h1-specific IgG4, Ara h2-specific IgG4, Ara h3-specificIgG4, Ara h6-specific IgG4, Ara h8-specific IgG4, or any other peanutallergen specific IgG4; or the level of peanut-specific IgG4 may be atotal of any one or more peanut levels of an allergen specific IgG4.

Exemplary Treatment Regimens

In some embodiments, the subject being treated for a food allergy isunlikely to tolerate oral immunotherapy, i.e., the subject is unlikelyto respond favorably to OIT alone. For instance, the subject beingtreated for peanut allergy may not be capable of tolerate about 1 mg orlower amounts of peanut allergens. In some embodiments, the subjectbeing treated for peanut allergy may not tolerate about 6 mg or higheramounts of peanut allergens. In other embodiments, the subject beingtreated for peanut allergy may not tolerate about 12 mg, 20 mg, 40 mg,80 mg, 120 mg, 160 mg, 200 mg, 240 mg, 300 mg, 400 mg, 500 mg, 600 mg,700 mg, 900 mg, 1200 mg, 1500 mg, 1800 mg, 2000 mg or higher amounts ofpeanut allergens.

The terms “a method for treating a subject suffering from a foodallergy,” “a method for desensitizing a subject suffering from a foodallergy,” and “a method for preventing or reducing the risk or severityof food allergy reaction in a subject” may be used interchangeablythroughout this application.

A food allergen is administered according to a dosing schedule. Thedosing schedule for an individual patient may vary depending on the age,health conditions, the nature and type of food allergen etc. Anexemplary dosing schedule for treating peanut allergy comprises: (a)administering to a subject suffering from peanut allergy escalatingdoses of about 0.5 mg, about 1.0 mg, about 1.5 mg, about 3.0 mg, andabout 6 mg of the peanut proteins in about 30 minute intervals on day 1;(b) optionally, administering a maximum tolerated dose (or a 3.0 mgdose) from day 1 for up to 2 weeks; and (c) administering single dosesof about 12 mg, about 20 mg, about 40 mg, about 80 mg, about 120 mg,about 160 mg, about 200 mg, about 240 mg, and about 300 mg of the peanutproteins at two week intervals.

Another exemplary dosing schedule for treating peanut allergy comprises:(a) administering to the subject escalating doses of about 0.5 mg, about1.0 mg, about 1.5 mg, about 3.0 mg, and about 6 mg of the peanutproteins in about 30-minute intervals on day 1; (b) optionally,administering a maximum tolerated dose from day 1 for up to 2 weeks; (c)administering single doses of about 12 mg, about 20 mg, about 40 mg,about 80 mg, about 120 mg, about 160 mg, about 200 mg, about 240 mg, andabout 300 mg of the peanut proteins at two week intervals up to 21weeks; (d) administering a maintenance dose of about 300 mg of thepeanut proteins for up to 24 weeks; and (e) administering single dosesof about 400 mg, about 475 mg, about 575 mg, about 775 mg, about 950 mg,about 1250 mg, about 1425 mg, about 1625 mg, and about 2000 mg at twoweek intervals.

U.S. Pre-grant Publication No. 2014/0271721 discloses oral immunotherapymethods and dosing schedules for treating peanut allergy; thispublication is incorporated by reference herein in its entirety for allpurposes.

Compositions/Formulations

Compositions and methods for treating peanut allergy are described indetail in U.S. Pre-grant Publication No. 2014/027172 and PCT PublicationNo. WO 2014/159609, both of which are incorporated by reference hereinin their entireties. Methods for preparing peanut protein formulationsare described in detail for U.S. Pre-grant Publication No. 2014/0271836,which is incorporated by reference herein in its entirety.

A composition for treating food allergy may comprise the food allergen,or alternatively, one or more proteins isolated from the food allergen,and optionally, may further comprise one or more diluents, one or moreglidants, and one or more lubricants. For instance, in one embodiment, acomposition for treating peanut allergy comprises peanut flour, oralternatively, one or more proteins isolated from peanut flour, one ormore diluents, one or more glidants, and one or more lubricants.

A composition for treating peanut allergy may contain, in one aspect,peanut flour, or alternatively, one or more proteins isolated frompeanut flour. In one embodiment, peanut flour comprises Arah1, Arah2 andArah6 proteins. In another embodiment, peanut flour contains as activeingredients: Arah1, Arah2 and Arah6 proteins.

In one embodiment, a final formulation for treating peanut allergy,comprises peanut flour (containing characterized peanut allergenproteins Ara h1, Ara h2 and Ara h6) formulated with a diluent, a glidantand a lubricant in graduated doses, comprising capsules containing 0.5mg, 1 mg, 10 mg, 100 mg, 475 mg, 500 mg, or 1000 mg of peanut flour.Each capsule may be opened and the content mixed into taste-masking foodimmediately prior to administration.

In another embodiment, a final formulation for treating peanut allergy,consists of peanut flour (containing characterized peanut allergenproteins Ara h1, Ara h2 and Ara h6) formulated with a bulking and a flowagent in graduated doses, comprising capsules containing 0.5 mg, 1 mg,10 mg, 100 mg, 475 mg, 500 mg, or 1000 mg of peanut flour. Each capsulemay be opened and the content mixed into taste-masking food immediatelyprior to administration.

In one embodiment, the dose of the composition for treating peanutallergy is 0.5 mg and the concentration of Ara h1 comprises from about0.035 to about 0.075 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 1.0 mg and the concentration of Ara h1 comprises from about0.075 to about 0.15 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 10.0 mg and the concentration of Ara h1 comprises from about0.5 to about 1.5 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 100.0 mg and the concentration of Ara h1 comprises from about7.5 to about 15 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 475 mg and the concentration of Ara h1 comprises from about35 to about 60 mg.

In one embodiment, dose of the composition for treating peanut allergyis 0.5 mg and the concentration of Ara h2 comprises from about 0.035 toabout 0.075 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 1.0 mg and the concentration of Ara h2 comprises from about0.075 to about 0.175 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 10.0 mg and the concentration of Ara h2 comprises from about0.5 to about 1.75 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 100.0 mg and the concentration of Ara h2 comprises from about7.5 to about 1.15 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 475 mg and the concentration of Ara h2 comprises from about45 to about 65 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 0.5 mg and the concentration of Ara h6 comprises from about0.015 to about 0.06 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 1.0 mg and the concentration of Ara h6 comprises from about0.025 to about 1.0 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 10.0 mg and the concentration of Ara h6 comprises from about0.35 to about 1.0 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 100.0 mg and the concentration of Ara h6 comprises from about3.5 to about 10 mg.

In another embodiment, the dose of the composition for treating peanutallergy is 475 mg and the concentration of Ara h6 comprises from about15 to 40 mg.

In yet another embodiment, the ratio of Ara h2: Ara h6 in a compositionfor treating peanut allergy is about 2.

Amounts of Ara h proteins are based upon peanut protein being about 50%w/w of the flour and the ratio of Ara h proteins in the extractableprotein is representative of the composition within the composition.

All patent and non-patent documents referenced throughout thisdisclosure are incorporated by reference herein in their entirety forall purposes.

Kits

Further provided herein are kits that include an allergenic peanutformulation or peanut composition as described herein and instructionsfor use. The instructions for use can instructions for any of themethods described herein, such as methods of treating a subject for apeanut allergy (for example by oral immunotherapy) including selectingthe subject for treatment based on having a level of peanut-specificIgEs at or below a predetermined threshold (such as about 100 kU/L);instructions for administering the composition or formulation to asubject with a peanut allergy, wherein the subject undergoes heightenedmonitoring for an allergic reaction if the peanut-specific IgEs in thesubject is above a predetermined threshold (such as about 100 kU/L); amethod of assessing the suitability of a treatment for a subject with apeanut allergy, wherein the subject having a level of peanut-specificIgEs at or below a predetermined threshold (such as about 100 kU/L)indicates that the treatment is suitable for the subject; a method forevaluating a symptom in a subject during the course of treatment of apeanut allergy, including determining whether the symptom is related tothe treatment, wherein a level of peanut-specific IgEs at or below apredetermined threshold indicates that the adverse event is not causedby the treatment; methods of monitoring treatment for a peanut allergyin a subject, including measuring a level of peanut-specific IgEs in thesubject during the course of treatment; a method of reducing the risk orincidence of an adverse event in a subject receiving treatment for apeanut allergy, including reducing a dose, delaying a dose, or delayingan increase of a dose of the allergenic peanut composition if the levelof peanut-specific IgEs is above a predetermined threshold; or a methodof adjusting a dose of an allergenic peanut composition, includingadministering a first dose of the allergenic peanut composition to asubject with a peanut allergy, receiving a level of peanut-specific IgEsin the subject after administration of the first dose, and administeringa second dose of the allergenic peanut composition to the subject,wherein the second dose is based on the first dose and the level ofpeanut-specific IgEs in the subject.

EXEMPLARY EMBODIMENTS

The following embodiments are exemplary and not intended to limit thescope of the invention described herein.

Embodiment 1

A method of treating a subject for a peanut allergy, comprising:

administering to the subject at least one dose of an allergenic peanutcomposition, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold.

Embodiment 2

A method of treating a subject for a peanut allergy, comprising:

selecting a subject for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; and

administering to the selected subject at least one dose of an allergenicpeanut composition.

Embodiment 3

A method of treating a subject for a peanut allergy, comprising:

measuring a level of peanut-specific IgEs for the subject;

selecting the subject for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; and

administering to the selected subject at least one dose of an allergenicpeanut composition.

Embodiment 4

A method of treating a subject for a peanut allergy, comprising:

measuring a level of peanut-specific IgEs for the subject prior to thestart of treatment;

selecting the subject for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold prior to thestart of treatment;

administering to the selected subject a plurality of doses of anallergenic peanut composition; and

monitoring the level of peanut-specific IgEs in the selected subjectduring the course of treatment.

Embodiment 5

A method of treating a subject for a peanut allergy, comprising:

measuring a level of peanut-specific IgEs for the subject prior to thestart of treatment;

selecting the subject for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold prior to thestart of treatment;

administering to the selected subject a plurality of doses of anallergenic peanut composition; and

monitoring the level of peanut-specific IgEs in the selected subjectduring the course of treatment, wherein:

(1) the subject undergoes heightened monitoring for an allergic reactionif the level of peanut-specific IgEs in the subject rises above thepredetermined threshold during the course of treatment; or

(2) reducing a dose, delaying a dose, or delaying a dose increase of theallergic peanut composition administered to the subject if the level ofpeanut-specific IgEs in the subject rises above the predeterminedthreshold during the course of treatment.

Embodiment 6

The method of any one of embodiments 1-5, wherein the predeterminedthreshold for the level of peanut-specific IgEs is about 100 kU/L.

Embodiment 7

The method of any one of embodiments 1-6, wherein the level ofpeanut-specific IgEs is determined prior to initiating treatment of thepeanut allergy.

Embodiment 8

The method of any one of embodiments 1-7, wherein the does isadministered to the subject as part of an oral immunotherapy dosingregimen.

Embodiment 9

The method of embodiment 8, wherein the dose is administered to thesubject during an initial escalation phase of the oral immunotherapydosing regimen.

Embodiment 10

The method of embodiment 9, wherein the dose is administered to thesubject during an up-dosing phase of the oral immunotherapy dosingregimen.

Embodiment 11

The method of embodiment 9, wherein the dose is administered to thesubject during a maintenance phase of the oral immunotherapy dosingregimen.

Embodiment 12

The method of any one of embodiments 1-11, comprising receiving thelevel of peanut-specific IgEs.

Embodiment 13

The method of any one of embodiments 1, 2, and 6-12, comprisingmeasuring the level of peanut-specific IgEs.

Embodiment 14

A method of treating a subject for a peanut allergy, comprising:

administering to the subject at least one dose of an allergenic peanutcomposition, wherein the subject undergoes heightened monitoring for anallergenic reaction if a level of peanut-specific IgEs in the subject isabove a predetermined threshold.

Embodiment 15

The method of embodiment 14, wherein the predetermined threshold of thelevel of peanut-specific IgEs is about 100 kU/L.

Embodiment 16

The method of embodiment 14 or 15, wherein heightened monitoringcomprises a longer clinical visit following administration of the dosecompared to a subject having a level of peanut-specific IgEs at or belowthe predetermined threshold.

Embodiment 17

The method of any one of embodiments 14-16, wherein heightenedmonitoring comprises active monitoring for the allergic reaction.

Embodiment 18

The method of embodiment 17, wherein active monitoring comprisesmeasuring a heart rate, blood pressure, respiratory rate, or bloodoxygen.

Embodiment 19

The method of any one of embodiments 14-18, wherein the allergicreaction is hypersensitivity, anaphylaxis, a gastrointestinal symptom,or eosinophilic esophagitis.

Embodiment 20

The method of any one of embodiments 14-19, wherein the dose isadministered to the subject as part of an oral immunotherapy dosingregimen.

Embodiment 21

The method of embodiment 20, wherein the dose is administered to thesubject during an initial escalation phase of the oral immunotherapyregimen.

Embodiment 22

The method of embodiment 20, wherein the dose is administered to thesubject during an up-dosing phase of an oral immunotherapy regimen.

Embodiment 23

The method of embodiment 20, wherein the dose is administered to thesubject during a maintenance phase of an oral immunotherapy regimen.

Embodiment 24

The method of any one of embodiments 14-23, comprising receiving thelevel of peanut-specific IgEs.

Embodiment 25

The method of any one of embodiments 14-24, comprising measuring thelevel of peanut-specific IgEs.

Embodiment 26

The method of any one of embodiments 14-25, wherein the level ofpeanut-specific IgEs in the subject is determine prior to initiatingtreatment of the subject.

Embodiment 27

The method of any one of embodiments 14-25, wherein the level ofpeanut-specific IgEs in the subject is determined during the course oftreatment.

Embodiment 28

A method of assessing the suitability of a treatment for a peanutallergy in a subject, comprising:

receiving a level of peanut-specific IgEs in the subject; and

assessing the suitability of the treatment, wherein the subject having alevel of peanut-specific IgEs at or below a predetermined thresholdindicates that the treatment is suitable for the subject.

Embodiment 29

The method of embodiment 28, wherein the predetermined threshold of thelevel of peanut-specific IgEs is about 100 kU/L.

Embodiment 30

The method of embodiment 28 or 29, wherein the treatment is an oralimmunotherapy dosage regimen.

Embodiment 31

The method of embodiment 30, comprising initiating administration of theoral immunotherapy dosage regimen to the subject.

Embodiment 32

The method of embodiment 31, wherein initiating administration of theoral immunotherapy dosage regimen to the subject comprises administeringan initial escalation phase of the oral immunotherapy regimen to thesubject.

Embodiment 33

The method of any one of embodiments 28-32, comprising measuring thelevel of peanut-specific IgEs in the subject.

Embodiment 34

A method of evaluating a symptom in a subject during the course oftreatment of a peanut allergy, comprising:

receiving a level of peanut-specific IgEs in the subject having anadverse event; and

determining whether the symptom is related to the treatment, wherein alevel of peanut-specific IgEs at or below a predetermined thresholdindicates that the adverse event is not caused by the treatment.

Embodiment 35

A method of evaluating a symptom in a subject during the course oftreatment of a peanut allergy, comprising:

administering to a subject a plurality of doses of an allergenic peanutcomposition;

receiving a level of peanut-specific IgEs in the subject having anadverse event; and

determining whether the symptom is related to the treatment, wherein alevel of peanut-specific IgEs at or below a predetermined thresholdindicates that the adverse event is not caused by the treatment; and

reducing a dose, delaying a dose, or delaying a dose increase of theallergenic peanut composition administered to the subject if the levelof peanut-specific IgEs in the subject is above the predeterminedthreshold.

Embodiment 36

The method of embodiment 34 or 35, wherein the level of peanut-specificIgE is determined prior to initiating the course of treatment.

Embodiment 37

The method of embodiment 34 or 35, wherein the level of peanut-specificIgE is determined during the course of treatment.

Embodiment 38

The method of embodiment 34 or 35, wherein the level of peanut-specificIgE is determined when the subject is symptomatic.

Embodiment 39

The method of any one of embodiments 34-38, wherein the predeterminedthreshold of the level of peanut-specific IgEs is about 100 kU/L.

Embodiment 40

The method of any one of embodiments 34-39, wherein the treatment is anoral immunotherapy dosage regimen.

Embodiment 41

The method of any one of embodiments 34-40, wherein the symptom is agastrointestinal symptom.

Embodiment 42

The method of embodiment 41, wherein the gastrointestinal symptom isvomiting or abdominal pain.

Embodiment 43

The method of any one of embodiments 34-42, comprising delaying a doseincrease during an up-dosing phase of the treatment if the symptom isdetermined to be related to the treatment.

Embodiment 44

The method of any one of embodiments 34-42, comprising reducing ordelaying a dose of an allergenic peanut composition administered to thesubject if the symptom is determined to be related to the treatment.

Embodiment 45

The method of any one of embodiments 34-42, comprising terminating thetreatment if the symptom is determined to be related to the treatment.

Embodiment 46

The method of any one of embodiments 34-45, comprising measuring thelevel of peanut-specific IgEs.

Embodiment 47

A method of monitoring treatment for a peanut allergy in a subject,comprising:

measuring a level of peanut-specific IgEs in the subject during thecourse of treatment.

Embodiment 48

The method of embodiment 47, wherein the treatment is an oralimmunotherapy dosage regimen.

Embodiment 49

The method of embodiment 47 or 48, comprising reducing or delaying adose of an allergenic peanut composition if the level of peanut-specificIgEs is above a predetermined threshold.

Embodiment 50

The method of embodiment 47 or 48, comprising delaying a dose increaseduring an up-dosing phase of the treatment if the level ofpeanut-specific IgEs is above a predetermined threshold.

Embodiment 51

The method of embodiment 47 or 48, comprising terminating the treatmentif the level of peanut-specific IgEs is above a predetermined threshold.

Embodiment 52

The method of embodiment 47 or 48, comprising increasing the dose if thelevel of peanut-specific IgEs is at or below a predetermined threshold.

Embodiment 53

The method of any one of embodiments 47-52, wherein the predeterminedthreshold is about 100 kU/L.

Embodiment 54

The method of any one of embodiment 47-53 wherein the level ofpeanut-specific IgEs is measured following an initial escalation phaseof the treatment.

Embodiment 55

The method of any one of embodiments 47-54, wherein the level ofpeanut-specific IgEs is measured during an up-dosing phase of thetreatment.

Embodiment 56

The method of any one of embodiments 47-55, wherein the level ofpeanut-specific IgEs is measured during a maintenance phase of thetreatment.

Embodiment 57

A method of reducing the risk or incidence of an adverse event in asubject receiving treatment for a peanut allergy, comprising:

receiving a level of peanut-specific IgEs in the subject; and

reducing a dose, delaying a dose, or delaying an increase of a dose ofan allergenic peanut composition if the level of peanut-specific IgEs isabove a predetermined threshold.

Embodiment 58

The method of embodiment 57, wherein the treatment is oralimmunotherapy.

Embodiment 59

The method of embodiment 57 or 58, wherein the predetermined level ofthe peanut-specific IgEs is about 100 kU/L.

Embodiment 60

The method of any one of embodiments 57-59, comprising measuring thelevel of peanut-specific IgEs in the subject.

Embodiment 61

The method of any one of embodiments 57-60, wherein the adverse event isan allergic reaction.

Embodiment 62

The method of any one of embodiments 57-61, comprising reducing the doseof the allergic peanut composition if the level of peanut-specific IgEsis above the predetermined threshold.

Embodiment 63

The method of embodiment 62, wherein the dose of the allergenic peanutcomposition is reduced during an up-dosing phase of the treatment.

Embodiment 64

The method of embodiment 62, wherein the dose of the allergenic peanutcomposition is reduced during a maintenance phase of the treatment.

Embodiment 65

The method of any one of embodiments 57-61, comprising delaying the doseof the allergic peanut composition if the level of peanut-specific IgEsis above the predetermined threshold.

Embodiment 66

The method of embodiment 65, wherein the dose is delayed during anup-dosing phase of the treatment.

Embodiment 67

The method of embodiment 65, wherein the dose is delayed during amaintenance phase of the treatment.

Embodiment 68

The method of any one of embodiments 57-61, comprising delaying theincrease of the dose of the allergic peanut composition during anup-dosing phase of the therapy if the level of peanut-specific IgEs isabove the predetermined threshold.

Embodiment 69

The method of any one of embodiments 57-68, comprising administering thedose to the subject.

Embodiment 70

A method of adjusting a dose of an allergenic peanut composition,comprising:

administering a first dose of the allergenic peanut composition to asubject with a peanut allergy;

receiving a level of peanut-specific IgEs in the subject afteradministration of the first dose; and

administering a second dose of the allergenic peanut composition to thesubject, wherein the second dose is based on the first dose and thelevel of peanut-specific IgEs in the subject.

Embodiment 71

The method of embodiment 70, wherein the second dose is lower than thefirst dose if the level of peanut-specific IgEs is above a predeterminedthreshold.

Embodiment 72

The method of embodiment 70 or 71, wherein the administration of thesecond dose is delayed if the level of peanut-specific IgEs is above apredetermined threshold.

Embodiment 73

The method of embodiment 70, wherein the second dose is the same as thefirst dose if the level of peanut-specific IgEs is above a predeterminedthreshold.

Embodiment 74

The method of embodiment 70, wherein the second dose is increasedrelative to the first dose if the level of peanut-specific IgEs is at orbelow the predetermined threshold.

Embodiment 75

The method of any one of embodiments 70-74, wherein the predeterminedthreshold is about 100 kU/L.

Embodiment 76

The method of any one of embodiments 70-75, comprising measuring thelevel of peanut-specific IgEs.

Embodiment 77

A method of monitoring treatment for a peanut allergy in a subject,comprising:

measuring a level of peanut-specific IgG4s or a peanut-specific IgE topeanut-specific IgG4 ratio in the subject during the course oftreatment.

Embodiment 78

The method of embodiment 77, comprising measuring the level ofpeanut-specific IgG4s in the subject during the course of treatment.

Embodiment 79

The method of embodiment 77, comprising measuring the peanut-specificIgE to peanut-specific IgG4 ratio in the subject during the course oftreatment.

Embodiment 80

The method of any one of embodiments 77-79, wherein the treatment is anoral immunotherapy dosing regimen.

Embodiment 81

The method of any one of embodiment 77-80 wherein the level ofpeanut-specific IgG4s or the peanut-specific IgE to peanut-specific IgG4ratio is measured following an initial escalation phase of thetreatment.

Embodiment 82

The method of any one of embodiments 77-81, wherein the level ofpeanut-specific IgG4s or the peanut-specific IgE to peanut-specific IgG4ratio is measured during an up-dosing phase of the treatment.

Embodiment 83

The method of any one of embodiments 77-82, wherein the level ofpeanut-specific IgG4s or the peanut-specific IgE to peanut-specific IgG4ratio is measured during a maintenance phase of the treatment.

Embodiment 84

The method of any one of embodiments 1-83, wherein the subject is ahuman.

Embodiment 85

The method of any one of embodiments 1-84, wherein the subject is about17 years of age or younger.

Embodiment 86

The method of embodiment 85, wherein the subject is about 4 years of ageto about 17 years of age.

Embodiment 87

The method of any one of embodiments 1-86, wherein the level ofpeanut-specific IgEs or the level of peanut-specific IgG4s correspondsto a level as measured by a fluorescence enzyme immunoassayauto-analyzer.

Embodiment 88

The method of any one of embodiments 1-87, wherein the level ofpeanut-specific IgEs or the level of peanut-specific IgG4s is measuredby a fluorescence enzyme immunoassay auto-analyzer.

Embodiment 89

A method of treating a subject suffering from a food allergy,comprising:

orally administering at least one dose of at least one allergen to thesubject according to a dosing schedule, wherein said patient isdetermined to be likely to tolerate oral immunotherapy based upon one ormore biomarkers as described herein.

Embodiment 90

The method of embodiment 89, wherein said treating is initiating oralimmunotherapy in the subject.

Embodiment 91

The method of embodiment 89 or 90, wherein the subject determined to belikely to respond favorably to the oral administration of the foodallergen has a food allergen-specific serum IgE level of about 0.35 kU/Lto about 17.4 kU/L, about 0.35 kU/L to about 50 kU/L, or about 0.35 kU/Lto about 99.9 kU/L.

Embodiment 92

The method of embodiment 89 or 90, wherein the subject determined to belikely to respond favorably to the oral administration of the foodallergen has a food allergen-specific serum IgE level of about 0.35 kU/Lto about 17.4 kU/L, about 0.35 kU/L to about 20 kU/L, about 0.35 kU/L toabout 25 kU/L, about 0.35 kU/L to about 30 kU/L, about 0.35 kU/L toabout 35 kU/L, about 0.35 kU/L to about to about 40 kU/L, about 0.35kU/L to about 45 kU/L, about 0.35 kU/L to about 50 kU/L, about 0.35 kU/Lto about 55 kU/L, about 0.35 kU/L to about 60 kU/L, about 0.35 kU/L toabout 65 kU/L, about 0.35 kU/L to about 70 kU/L, about 0.35 kU/L toabout 75 kU/L, about 0.35 kU/L to about 80 kU/L, about 0.35 kU/L toabout 85 kU/L, about 0.35 kU/L to about 90 kU/L, about 0.35 kU/L toabout 95 kU/L, or about 0.35 kU/L to about 99 kU/L.

Embodiment 93

The method of embodiments 89 or 90, wherein the subject determined to belikely to respond favorably to the oral administration of the foodallergen has a food allergen-specific serum IgE level of about 0.35 kU/Lto about 125 kU/L, about 0.35 kU/L to about 150 kU/L, about 0.35 kU/L toabout 175 kU/L, about 0.35 kU/L to about 200 kU/L, about 0.35 kU/L toabout 225 kU/L, about 0.35 kU/L to about 250 kU/L, about 0.35 kU/L toabout 275 kU/L, about 0.35 kU/L to about 300 kU/L, about 0.35 kU/L toabout 325 kU/L, about 0.35 kU/L to about 350 kU/L, about 0.35 kU/L toabout 375 kU/L, about 0.35 kU/L to about 400 kU/L, about 0.35 kU/L toabout 425 kU/L, or about 0.35 kU/L to about 450 kU/L.

Embodiment 94

A method of treating a subject suffering from a food allergy,comprising:

orally administering at least one dose of at least one allergen to thesubject according to a dosing schedule, and coadministering atherapeutic agent that is an antagonist of one or more immunologicalmediators of allergy, wherein said patient is determined to be unlikelyto tolerate oral immunotherapy based upon one or more biomarkers asdescribed herein.

Embodiment 95

The method of embodiment 94, wherein the subject unlikely to respondfavorably to the oral administration of the food allergen has a foodallergen-specific serum IgE level of about 50 kU/L or more, about 55kU/L or more, about 60 kU/L or more, about 65 kU/L or more, about 70kU/L or more, about 75 kU/L or more, about 80 kU/L or more, about 85kU/L or more, about 90 kU/L or more, about 95 kU/L or more, or about 100kU/L or more, about 125 kU/L or more, about 150 kU/L or more, about 175kU/L or more, about 200 kU/L or more, about 225 kU/L or more, about 250kU/L or more, about 275 kU/L or more, about 300 kU/L or more, about 325kU/L or more, about 350 kU/L or more, about 375 kU/L or more, or about400 kU/L or more.

Embodiment 96

The method of embodiment 94 or 95, wherein the subject unlikely torespond favorably to the oral administration of the food allergen has afood allergen-specific serum IgE level of about 100 kU/L or more.

Embodiment 97

The method of any one of embodiments 89-96, wherein the subject isallergic to one or more peanut allergens.

Embodiment 98

The method of any one of embodiments 89-97, wherein the subjectsuffering from a food allergy is likely or unlikely to respond favorablyto the oral administration of the food allergen based on the levels ofone or more biomarkers selected from the group consisting of: total IgE,allergen-specific IgE, allergen-specific IgG4, ratio of IgG to IgE, theratio of allergen-specific IgE to IgG4, and cell surface markers onimmune cells.

Embodiment 99

The method of any one of embodiments 89-97, wherein the subject isallergic to one or more peanut allergens and is likely or unlikely torespond favorably to the oral administration of the peanut allergenbased on the levels of one or more biomarkers selected from the groupconsisting of: total IgE, peanut-specific IgE, Ara h1-specific IgE, Arah2-specific IgE, Ara h3-specific IgE, Ara h8-specific IgE, Arah9-specific IgE, peanut-specific IgG4, ratio of IgG to IgE, the ratio ofallergen-specific IgE to IgG4 and cell surface markers on immune cells.

Embodiment 100

The method of any one of embodiments 94-99, wherein the therapeuticagent is an IgE antagonist.

Embodiment 101

The method of any one of embodiments 89-100, wherein the at least onedose of at least one allergen is an allergen composition comprising oneor more peanut proteins.

Embodiment 102

The method of embodiment 101, wherein the allergen composition comprisesone or more characterized peanut proteins and pharmaceuticallyacceptable excipients.

Embodiment 103

The method of any one of embodiments 89-102, wherein the dosing schedulecomprises:

(a) administering to the subject escalating doses of about 0.5 mg, about1.0 mg, about 1.5 mg, about 3.0 mg, and about 6 mg of the peanutproteins in about 30-minute intervals on day 1;

(b) optionally, administering a maximum tolerated dose or about 3 mg ofthe peanut proteins from day 1 for up to 2 weeks; and

(c) administering single doses of about 12 mg, about 20 mg, about 40 mg,about 80 mg, about 120 mg, about 160 mg, about 200 mg, about 240 mg, andabout 300 mg of the peanut proteins at two week intervals.

Embodiment 104

The method of any one of embodiments 89-103, wherein the dosing schedulecomprises:

(a) administering to the subject escalating doses of about 0.5 mg, about1.0 mg, about 1.5 mg, about 3.0 mg, and about 6 mg of the peanutproteins in about 30-minute intervals on day 1;

(b) optionally, administering a maximum tolerated dose or about 3 mg ofthe peanut proteins from day 1 for up to 2 weeks;

(c) administering single doses of about 12 mg, about 20 mg, about 40 mg,about 80 mg, about 120 mg, about 160 mg, about 200 mg, about 240 mg, andabout 300 mg of the peanut proteins at two week intervals to 21 weeks;

(d) administering a maintenance dose of about 300 mg of the peanutproteins for up to 24 weeks; and

(e) administering single doses of about 400 mg, about 475 mg, about 575mg, about 775 mg, about 950 mg, about 1250 mg, about 1425 mg, about 1625mg, and about 2000 mg at two week intervals.

Embodiment 105

A method of diagnosing a subject suffering from a food allergy as likelyor unlikely to respond favorably to oral immunotherapy comprising,measuring levels of one or more biomarkers in the subject selected fromthe group consisting of: total IgE, allergen-specific IgE,allergen-specific IgG4, ratio of IgG to IgE, and the ratio ofallergen-specific IgE to IgG4, cell surface markers on immune cells, andcombinations thereof.

Embodiment 106

A method of diagnosing a subject suffering from a peanut allergy aslikely or unlikely to respond favorably to oral immunotherapycomprising, measuring levels of one or more biomarkers in the subjectselected from the group consisting of: total IgE, peanut-specific IgE,Ara h1-specific IgE, Ara h2-specific IgE, Ara h3-specific IgE, Arah8-specific IgE, Ara h9-specific IgE, peanut-specific IgG4, ratio of IgGto IgE, the ratio of allergen-specific IgE to IgG4 and cell surfacemarkers on immune cells.

Embodiment 107

The method of embodiment 106, wherein the subject suffering from thepeanut allergy is diagnosed as incapable of responding favorably to oralimmunotherapy alone when the subject has a peanut-specific serum IgElevel of about 100 kU/L or more, about 125 kU/L or more, about 150 kU/Lor more, about 175 kU/L or more, about 200 kU/L or more, about 225 kU/Lor more, about 250 kU/L or more, about 275 kU/L or more, about 300 kU/Lor more, about 325 kU/L or more, about 350 kU/L or more, about 375 kU/Lor more, or about 400 kU/L or more.

Embodiment 108

A method of treating a subject suffering from a peanut allergy,comprising: orally administering at least one dose of at least oneallergen to the subject according to a dosing schedule, andcoadministering a therapeutic agent that is an antagonist of one or moreimmunological mediators of allergy, wherein the subject has apeanut-specific serum IgE level of about 100 kU/L or more, about 125kU/L or more, about 150 kU/L or more, about 175 kU/L or more, about 200kU/L or more, about 225 kU/L or more, about 250 kU/L or more, about 275kU/L or more, about 300 kU/L or more, about 325 kU/L or more, about 350kU/L or more, about 375 kU/L or more, or about 400 kU/L or more.

Embodiment 109

The method of embodiment 108, wherein the therapeutic agent is an IgEantagonist.

Embodiment 110

The method of embodiment 100 or 109, wherein the IgE antagonist isomalizumab.

Embodiment 111

A method of assessing a likelihood of an allergic reaction that requiresadministration of epinephrine to a subject receiving treatment for apeanut allergy, wherein the treatment comprises administration of atleast one dose of an allergenic peanut composition, the methodcomprising:

receiving a level of peanut-specific IgEs in the subject; and

assessing the likelihood of an allergic reaction that requiresadministration of epinephrine to the patient, wherein a level ofpeanut-specific IgEs at or below a predetermined threshold indicates areduced likelihood of an allergic reaction that requires administrationof epinephrine during treatment, and wherein a level of peanut-specificIgEs above the predetermined threshold indicates an increased likelihoodof an allergic reaction that requires administration of epinephrineduring treatment.

Embodiment 112

A method of assessing a likelihood of an allergic reaction that requiresadministration of epinephrine to a subject receiving treatment for apeanut allergy, wherein the treatment comprises administration of atleast one dose of an allergenic peanut composition, the methodcomprising:

receiving a level of peanut-specific IgEs in the subject; and

assessing the likelihood of an allergic reaction that requiresadministration of epinephrine to the patient, wherein a level ofpeanut-specific IgEs at or below a predetermined threshold indicates areduced likelihood of an allergic reaction that requires administrationof epinephrine during treatment, and wherein a level of peanut-specificIgEs above the predetermined threshold indicates an increased likelihoodof an allergic reaction that requires administration of epinephrineduring treatment; and

administering to the subject one or more doses of an allergenic peanutcomposition if the level of peanut-specific IgEs is at or below thepredetermined threshold.

Embodiment 113

The method of embodiment 111 or 112, wherein the predetermined thresholdof the level of peanut-specific IgEs is about 100 kU/L.

Embodiment 114

The method of any one of embodiments 111-113, wherein the treatment isan oral immunotherapy dosing regimen.

Embodiment 115

The method of any one of embodiments 111-114, further comprisingadministering to the subject at least one dose of an allergenic peanutcomposition.

Embodiment 116

The method of any one of embodiments 111-115, wherein the subject is ahuman.

Embodiment 117

The method of any one of embodiments 111-116, wherein the subject isabout 17 years of age or younger.

Embodiment 118

The method of embodiment 117, wherein the subject is about 4 years ofage to about 17 years of age.

Embodiment 119

The method of any one of embodiments 111-118, comprising recommending tothe subject that the subject have immediate access to at least two dosesof injectable epinephrine for treatment of the allergic reaction if thesubject has a level of peanut-specific IgEs above the predeterminedthreshold.

Embodiment 120

The method of embodiment 119, wherein each dose of epinephrine is about0.15 mg of injectable epinephrine if the subject weighs less than about30 kilograms, or about 0.3 mg of injectable epinephrine if the subjectweighs about 30 kilograms or more.

Embodiment 121

The method of any one of embodiments 111-120, comprising measuring thelevel of peanut-specific IgEs in the subject prior to initiatingtreatment for the peanut allergy.

Embodiment 122

The method of any one of embodiments 111-121, wherein the level ofpeanut-specific IgEs in the subject is a level determined prior toinitiating treatment of the peanut allergy.

Embodiment 123

The method of any one of embodiments 111-122, wherein the level ofpeanut-specific IgEs in the subject is a level determined during thecourse of treatment.

Embodiment 124

The method of any one of embodiments 111-123, wherein the level ofpeanut-specific IgEs corresponds to a level as measured by afluorescence enzyme immunoassay auto-analyzer.

Embodiment 125

The method of any one of embodiments 111-124, wherein the level ofpeanut-specific IgEs is measured by a fluorescence enzyme immunoassayauto-analyzer.

Embodiment 126

A method of treating a subject for an allergy to an allergenic food,comprising:

administering to the subject at least one dose of an allergenic foodcomposition, wherein the subject is selected for treatment based onhaving a level of allergenic food-specific IgEs at or below apredetermined threshold.

Embodiment 127

A method of treating a subject for an allergy to an allergenic food,comprising:

selecting a subject for treatment based on having a level of allergenicfood-specific IgEs at or below a predetermined threshold; and

administering to the selected subject at least one dose of an allergenicfood composition.

Embodiment 128

A method of treating a subject for an allergy to an allergenic food,comprising:

measuring a level of allergenic food-specific IgEs for the subject;

selecting the subject for treatment based on having a level ofallergenic food-specific IgEs at or below a predetermined threshold; and

administering to the selected subject at least one dose of an allergenicfood composition.

Embodiment 129

A method of treating a subject for an allergy to an allergenic food,comprising:

measuring a level of allergenic food-specific IgEs for the subject priorto the start of treatment;

selecting the subject for treatment based on having a level ofallergenic food-specific IgEs at or below a predetermined thresholdprior to the start of treatment;

administering to the selected subject a plurality of doses of anallergenic food composition; and

monitoring the level of allergenic food-specific IgEs in the selectedsubject during the course of treatment.

Embodiment 130

A method of treating a subject for an allergy to an allergenic food,comprising:

measuring a level of allergenic food-specific IgEs for the subject priorto the start of treatment;

selecting the subject for treatment based on having a level ofallergenic food-specific IgEs at or below a predetermined thresholdprior to the start of treatment;

administering to the selected subject a plurality of doses of anallergenic food composition; and

monitoring the level of allergenic food-specific IgEs in the selectedsubject during the course of treatment, wherein:

(1) the subject undergoes heightened monitoring for an allergic reactionif the level of allergenic food-specific IgEs in the subject rises abovethe predetermined threshold during the course of treatment; or

(2) reducing a dose, delaying a dose, or delaying a dose increase of theallergic food composition administered to the subject if the level ofallergenic food-specific IgEs in the subject rises above thepredetermined threshold during the course of treatment.

Embodiment 131

The method of any one of embodiments 126-130, wherein the predeterminedthreshold for the level of allergenic food-specific IgEs is about 100kU/L.

Embodiment 132

The method of any one of embodiments 126-131, wherein the level ofallergenic food-specific IgEs is determined prior to initiatingtreatment of the allergy to the allergenic food.

Embodiment 133

The method of any one of embodiments 126-132, wherein the does isadministered to the subject as part of an oral immunotherapy dosingregimen.

Embodiment 134

The method of embodiment 133, wherein the dose is administered to thesubject during an initial escalation phase of the oral immunotherapydosing regimen.

Embodiment 135

The method of embodiment 133, wherein the dose is administered to thesubject during an up-dosing phase of the oral immunotherapy dosingregimen.

Embodiment 136

The method of embodiment 133, wherein the dose is administered to thesubject during a maintenance phase of the oral immunotherapy dosingregimen.

Embodiment 137

The method of any one of embodiments 126-136, comprising receiving thelevel of allergenic food-specific IgEs.

Embodiment 138

The method of any one of embodiments 126, 27, and 131-137, comprisingmeasuring the level of allergenic food-specific IgEs.

Embodiment 139

A method of treating a subject for an allergy to a food allergy,comprising:

administering to the subject at least one dose of an allergenic foodcomposition, wherein the subject undergoes heightened monitoring for anallergenic reaction if a level of allergenic food-specific IgEs in thesubject is above a predetermined threshold.

Embodiment 140

The method of embodiment 139, wherein the predetermined threshold of thelevel of allergenic food-specific IgEs is about 100 kU/L.

Embodiment 141

The method of embodiment 139 or 140, wherein heightened monitoringcomprises a longer clinical visit following administration of the dosecompared to a subject having a level of allergenic food-specific IgEs ator below the predetermined threshold.

Embodiment 142

The method of any one of embodiments 139-141, wherein heightenedmonitoring comprises active monitoring for the allergic reaction.

Embodiment 143

The method of embodiment 142, wherein active monitoring comprisesmeasuring a heart rate, blood pressure, respiratory rate, or bloodoxygen.

Embodiment 144

The method of any one of embodiments 139-143, wherein the allergicreaction is hypersensitivity, anaphylaxis, a gastrointestinal symptom,or eosinophilic esophagitis.

Embodiment 145

The method of any one of embodiments 139-144, wherein the dose isadministered to the subject as part of an oral immunotherapy dosingregimen.

Embodiment 146

The method of embodiment 145, wherein the dose is administered to thesubject during an initial escalation phase of the oral immunotherapyregimen.

Embodiment 147

The method of embodiment 145, wherein the dose is administered to thesubject during an up-dosing phase of an oral immunotherapy regimen.

Embodiment 148

The method of embodiment 145, wherein the dose is administered to thesubject during a maintenance phase of an oral immunotherapy regimen.

Embodiment 149

The method of any one of embodiments 139-148, comprising receiving thelevel of allergenic food-specific IgEs.

Embodiment 150

The method of any one of embodiments 139-149, comprising measuring thelevel of allergenic food-specific IgEs.

Embodiment 151

The method of any one of embodiments 139-150, wherein the level ofallergenic food-specific IgEs in the subject is determine prior toinitiating treatment of the subject.

Embodiment 152

The method of any one of embodiments 139-150, wherein the level ofallergenic food-specific IgEs in the subject is determined during thecourse of treatment.

Embodiment 153

A method of assessing the suitability of a treatment for an allergy toan allergenic food in a subject, comprising:

receiving a level of allergenic food-specific IgEs in the subject; and

assessing the suitability of the treatment, wherein the subject having alevel of allergenic food-specific IgEs at or below a predeterminedthreshold indicates that the treatment is suitable for the subject.

Embodiment 154

The method of embodiment 153, wherein the predetermined threshold of thelevel of allergenic food-specific IgEs is about 100 kU/L.

Embodiment 155

The method of embodiment 153 or 154, wherein the treatment is an oralimmunotherapy dosage regimen.

Embodiment 156

The method of embodiment 155, comprising initiating administration ofthe oral immunotherapy dosage regimen to the subject.

Embodiment 157

The method of embodiment 156, wherein initiating administration of theoral immunotherapy dosage regimen to the subject comprises administeringan initial escalation phase of the oral immunotherapy regimen to thesubject.

Embodiment 158

The method of any one of embodiments 153-157, comprising measuring thelevel of allergenic food-specific IgEs in the subject.

Embodiment 159

A method of evaluating a symptom in a subject during the course oftreatment of an allergy for an allergenic food, comprising:

receiving a level of allergenic food-specific IgEs in the subject havingan adverse event; and

determining whether the symptom is related to the treatment, wherein alevel of allergenic food-specific IgEs at or below a predeterminedthreshold indicates that the adverse event is not caused by thetreatment.

Embodiment 160

A method of evaluating a symptom in a subject during the course oftreatment of an allergy for an allergenic food, comprising:

administering to a subject a plurality of doses of an allergenic foodcomposition;

receiving a level of allergenic food-specific IgEs in the subject havingan adverse event; and

determining whether the symptom is related to the treatment, wherein alevel of allergenic food-specific IgEs at or below a predeterminedthreshold indicates that the adverse event is not caused by thetreatment; and

reducing a dose, delaying a dose, or delaying a dose increase of theallergenic food composition administered to the subject if the level ofallergenic food-specific IgEs in the subject is above the predeterminedthreshold.

Embodiment 161

The method of embodiment 159 or 160, wherein the level of allergenicfood-specific IgE is determined prior to initiating the course oftreatment.

Embodiment 162

The method of embodiment 159 or 160, wherein the level of allergenicfood-specific IgE is determined during the course of treatment.

Embodiment 163

The method of embodiment 159 or 160, wherein the level of allergenicfood-specific IgE is determined when the subject is symptomatic.

Embodiment 164

The method of any one of embodiments 159-163, wherein the predeterminedthreshold of the level of allergenic food-specific IgEs is about 100kU/L.

Embodiment 165

The method of any one of embodiments 159-164, wherein the treatment isan oral immunotherapy dosage regimen.

Embodiment 166

The method of any one of embodiments 159-165, wherein the symptom is agastrointestinal symptom.

Embodiment 167

The method of embodiment 166, wherein the gastrointestinal symptom isvomiting or abdominal pain.

Embodiment 168

The method of any one of embodiments 159-167, comprising delaying a doseincrease during an up-dosing phase of the treatment if the symptom isdetermined to be related to the treatment.

Embodiment 169

The method of any one of embodiments 159-167, comprising reducing ordelaying a dose of an allergenic food composition administered to thesubject if the symptom is determined to be related to the treatment.

Embodiment 170

The method of any one of embodiments 159-167, comprising terminating thetreatment if the symptom is determined to be related to the treatment.

Embodiment 171

The method of any one of embodiments 159-170, comprising measuring thelevel of allergenic food-specific IgEs.

Embodiment 172

A method of monitoring treatment for an allergy for an allergenic foodin a subject, comprising:

measuring a level of allergenic food-specific IgEs in the subject duringthe course of treatment.

Embodiment 173

The method of embodiment 172, wherein the treatment is an oralimmunotherapy dosage regimen.

Embodiment 174

The method of embodiment 172 or 173, comprising reducing or delaying adose of an allergenic food composition if the level of allergenicfood-specific IgEs is above a predetermined threshold.

Embodiment 175

The method of embodiment 172 or 173, comprising delaying a dose increaseduring an up-dosing phase of the treatment if the level of allergenicfood-specific IgEs is above a predetermined threshold.

Embodiment 176

The method of embodiment 172 or 173, comprising terminating thetreatment if the level of allergenic food-specific IgEs is above apredetermined threshold.

Embodiment 177

The method of embodiment 172 or 173, comprising increasing the dose ifthe level of allergenic food-specific IgEs is at or below apredetermined threshold.

Embodiment 178

The method of any one of embodiments 172-177, wherein the predeterminedthreshold is about 100 kU/L.

Embodiment 179

The method of any one of embodiment 172-178 wherein the level ofallergenic food-specific IgEs is measured following an initialescalation phase of the treatment.

Embodiment 180

The method of any one of embodiments 172-179, wherein the level ofallergenic food-specific IgEs is measured during an up-dosing phase ofthe treatment.

Embodiment 181

The method of any one of embodiments 172-180, wherein the level ofallergenic food-specific IgEs is measured during a maintenance phase ofthe treatment.

Embodiment 182

A method of reducing the risk or incidence of an adverse event in asubject receiving treatment for a food allergy, comprising:

receiving a level of allergenic food-specific IgEs in the subject; and

reducing a dose, delaying a dose, or delaying an increase of a dose ofan allergenic food composition if the level of allergenic food-specificIgEs is above a predetermined threshold.

Embodiment 183

The method of embodiment 182, wherein the treatment is oralimmunotherapy.

Embodiment 184

The method of embodiment 182 or 183, wherein the predetermined level ofthe allergenic food-specific IgEs is about 100 kU/L.

Embodiment 185

The method of any one of embodiments 182-184, comprising measuring thelevel of allergenic food-specific IgEs in the subject.

Embodiment 186

The method of any one of embodiments 182-185, wherein the adverse eventis an allergic reaction.

Embodiment 187

The method of any one of embodiments 182-186, comprising reducing thedose of the allergic food composition if the level of allergenicfood-specific IgEs is above the predetermined threshold.

Embodiment 188

The method of embodiment 187, wherein the dose of the allergenic foodcomposition is reduced during an up-dosing phase of the treatment.

Embodiment 189

The method of embodiment 187, wherein the dose of the allergenic foodcomposition is reduced during a maintenance phase of the treatment.

Embodiment 190

The method of any one of embodiments 182-189, comprising delaying thedose of the allergic food composition if the level of allergenicfood-specific IgEs is above the predetermined threshold.

Embodiment 191

The method of embodiment 190, wherein the dose is delayed during anup-dosing phase of the treatment.

Embodiment 192

The method of embodiment 190, wherein the dose is delayed during amaintenance phase of the treatment.

Embodiment 193

The method of any one of embodiments 182-192, comprising delaying theincrease of the dose of the allergic food composition during anup-dosing phase of the therapy if the level of allergenic food-specificIgEs is above the predetermined threshold.

Embodiment 194

The method of any one of embodiments 182-193, comprising administeringthe dose to the subject.

Embodiment 195

A method of adjusting a dose of an allergenic food composition,comprising:

administering a first dose of the allergenic food composition to asubject with a food allergy;

receiving a level of allergenic food-specific IgEs in the subject afteradministration of the first dose; and

administering a second dose of the allergenic food composition to thesubject, wherein the second dose is based on the first dose and thelevel of allergenic food-specific IgEs in the subject.

Embodiment 196

The method of embodiment 195, wherein the second dose is lower than thefirst dose if the level of allergenic food-specific IgEs is above apredetermined threshold.

Embodiment 197

The method of embodiment 195 or 196, wherein the administration of thesecond dose is delayed if the level of allergenic food-specific IgEs isabove a predetermined threshold.

Embodiment 198

The method of embodiment 195, wherein the second dose is the same as thefirst dose if the level of allergenic food-specific IgEs is above apredetermined threshold.

Embodiment 199

The method of embodiment 195, wherein the second dose is increasedrelative to the first dose if the level of allergenic food-specific IgEsis at or below the predetermined threshold.

Embodiment 200

The method of any one of embodiments 195-199, wherein the predeterminedthreshold is about 100 kU/L.

Embodiment 201

The method of any one of embodiments 195-200, comprising measuring thelevel of allergenic food-specific IgEs.

Embodiment 202

A method of monitoring treatment for a allergy to an allergenic food ina subject, comprising:

measuring a level of allergenic food-specific IgG4s or an allergenicfood-specific IgE to allergenic food-specific IgG4 ratio in the subjectduring the course of treatment.

Embodiment 203

The method of embodiment 202, comprising measuring the level ofallergenic food-specific IgG4s in the subject during the course oftreatment.

Embodiment 204

The method of embodiment 202, comprising measuring the allergenicfood-specific IgE to allergenic food-specific IgG4 ratio in the subjectduring the course of treatment.

Embodiment 205

The method of any one of embodiments 202-204, wherein the treatment isan oral immunotherapy dosing regimen.

Embodiment 206

The method of any one of embodiment 202-205 wherein the level ofallergenic food-specific IgG4s or the allergenic food-specific IgE toallergenic food-specific IgG4 ratio is measured following an initialescalation phase of the treatment.

Embodiment 207

The method of any one of embodiments 202-206, wherein the level ofallergenic food-specific IgG4s or the allergenic food-specific IgE toallergenic food-specific IgG4 ratio is measured during an up-dosingphase of the treatment.

Embodiment 208

The method of any one of embodiments 202-207, wherein the level ofallergenic food-specific IgG4s or the allergenic food-specific IgE toallergenic food-specific IgG4 ratio is measured during a maintenancephase of the treatment.

Embodiment 209

A method of assessing a likelihood of an allergic reaction that requiresadministration of epinephrine to a subject receiving treatment for afood allergy, wherein the treatment comprises administration of at leastone dose of an allergenic food composition, the method comprising:

receiving a level of allergenic food-specific IgEs in the subject; and

assessing the likelihood of an allergic reaction that requiresadministration of epinephrine to the patient, wherein a level ofallergenic food-specific IgEs at or below a predetermined thresholdindicates a reduced likelihood of an allergic reaction that requiresadministration of epinephrine during treatment, and wherein a level ofallergenic food-specific IgEs above the predetermined thresholdindicates an increased likelihood of an allergic reaction that requiresadministration of epinephrine during treatment.

Embodiment 210

A method of assessing a likelihood of an allergic reaction that requiresadministration of epinephrine to a subject receiving treatment for afood allergy, wherein the treatment comprises administration of at leastone dose of an allergenic food composition, the method comprising:

receiving a level of allergenic food-specific IgEs in the subject; and

assessing the likelihood of an allergic reaction that requiresadministration of epinephrine to the patient, wherein a level ofallergenic food-specific IgEs at or below a predetermined thresholdindicates a reduced likelihood of an allergic reaction that requiresadministration of epinephrine during treatment, and wherein a level ofallergenic food-specific IgEs above the predetermined thresholdindicates an increased likelihood of an allergic reaction that requiresadministration of epinephrine during treatment; and

administering to the subject one or more doses of an allergenic foodcomposition if the level of allergenic food-specific IgEs is at or belowthe predetermined threshold.

Embodiment 211

The method of embodiment 209 or 210, wherein the predetermined thresholdof the level of allergenic food-specific IgEs is about 100 kU/L.

Embodiment 212

The method of any one of embodiments 209-211, wherein the treatment isan oral immunotherapy dosing regimen.

Embodiment 213

The method of any one of embodiments 209-212, further comprisingadministering to the subject at least one dose of an allergenic foodcomposition.

Embodiment 214

The method of any one of embodiments 209-213, comprising recommending tothe subject that the subject have immediate access to at least two dosesof injectable epinephrine for treatment of the allergic reaction if thesubject has a level of allergenic food-specific IgEs above thepredetermined threshold.

Embodiment 215

The method of embodiment 214, wherein each dose of epinephrine is about0.15 mg of injectable epinephrine if the subject weighs less than about30 kilograms, or about 0.3 mg of injectable epinephrine if the subjectweighs about 30 kilograms or more.

Embodiment 216

The method of any one of embodiments 209-215, comprising measuring thelevel of allergenic food-specific IgEs in the subject prior toinitiating treatment for the food allergy.

Embodiment 217

The method of any one of embodiments 209-216, wherein the level ofallergenic food-specific IgEs in the subject is a level determined priorto initiating treatment of the food allergy.

Embodiment 218

The method of any one of embodiments 209-216, wherein the level ofallergenic food-specific IgEs in the subject is a level determinedduring the course of treatment.

Embodiment 219

The method of any one of embodiments 126-218, wherein the subject is ahuman.

Embodiment 220

The method of any one of embodiments 126-219, wherein the subject isabout 17 years of age or younger.

Embodiment 221

The method of embodiment 220, wherein the subject is about 4 years ofage to about 17 years of age.

Embodiment 222

The method of any one of embodiments 126-221, wherein the level ofallergenic food-specific IgEs or the level of allergenic food-specificIgG4s corresponds to a level as measured by a fluorescence enzymeimmunoassay auto-analyzer.

Embodiment 223

The method of any one of embodiments 126-222, wherein the level ofallergenic food-specific IgEs or the level of allergenic food-specificIgG4s is measured by a fluorescence enzyme immunoassay auto-analyzer.

Embodiments 224

The method of any one of embodiments 1-223, wherein the level of thebiomarker, the level of the peanut-specific IgE, the level of theallergenic food-specific IgE, the level of the peanut-specific IgG4,and/or the level of the allergenic food-specific IgG4 is determined invitro.

Embodiment 225

An allergenic peanut composition for use in treating a subject for apeanut allergy, wherein at least one dose of an allergenic peanutcomposition is administered to the subject, wherein the subject isselected for treatment based on having a level of peanut-specific IgEsat or below a predetermined threshold.

Embodiment 226

An allergenic peanut composition for use in treating a subject for apeanut allergy, wherein a subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold; and wherein at least one dose of the allergenic peanutcomposition is administered to the subject.

Embodiment 227

An allergenic peanut composition for use in treating a subject for apeanut allergy, wherein a level of peanut-specific IgEs for the subjectis measured in vitro; the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold; and at least one dose of an allergenic peanut composition isadministered to the selected subject.

Embodiment 228

An allergenic peanut composition for use in treating a subject for apeanut allergy, wherein a level of peanut-specific IgEs for the subjectis measured in vitro; the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold; at least one dose of an allergenic peanut composition isadministered to the selected subject; and the level of peanut-specificIgEs in the selected subject is monitored in vitro during the course oftreatment.

Embodiment 229

An allergenic peanut composition for use in treating a subject for apeanut allergy, wherein a level of peanut-specific IgEs for the subjectis measured in vitro; the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold; at least one dose of an allergenic peanut composition isadministered to the selected subject; and the level of peanut-specificIgEs in the selected subject is monitored in vitro during the course oftreatment; and wherein (1) the subject undergoes heightened monitoringfor an allergic reaction if the level of peanut-specific IgEs in thesubject rises above the predetermined threshold during the course oftreatment; or (2) a dose of the allergenic peanut composition isreduced, a dose of the allergenic peanut composition administered to thesubject is delayed, or an increase of a dose of the allergeniccomposition is delayed if the level of peanut-specific IgEs in thesubject rises above the predetermined threshold during the course oftreatment.

Embodiment 230

Use of an allergenic peanut composition in the manufacture of amedicament for treating a subject for a peanut allergy, wherein at leastone dose of an allergenic peanut composition is administered to thesubject, wherein the subject is selected for treatment based on having alevel of peanut-specific IgEs at or below a predetermined threshold.

Embodiment 231

Use of an allergenic peanut composition in the manufacture of amedicament for treating a subject for a peanut allergy, wherein asubject is selected for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; and whereinat least one dose of the allergenic peanut composition is administeredto the subject.

Embodiment 232

Use of an allergenic peanut composition in the manufacture of amedicament for treating a subject for a peanut allergy, wherein a levelof peanut-specific IgEs for the subject is measured in vitro; thesubject is selected for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; and at leastone dose of an allergenic peanut composition is administered to theselected subject.

Embodiment 233

Use of an allergenic peanut composition in the manufacture of amedicament for treating a subject for a peanut allergy, wherein a levelof peanut-specific IgEs for the subject is measured in vitro; thesubject is selected for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; at least onedose of an allergenic peanut composition is administered to the selectedsubject; and the level of peanut-specific IgEs in the selected subjectis monitored in vitro during the course of treatment.

Embodiment 234

Use of an allergenic peanut composition in the manufacture of amedicament for treating a subject for a peanut allergy, wherein a levelof peanut-specific IgEs for the subject is measured in vitro; thesubject is selected for treatment based on having a level ofpeanut-specific IgEs at or below a predetermined threshold; at least onedose of an allergenic peanut composition is administered to the selectedsubject; and the level of peanut-specific IgEs in the selected subjectis monitored in vitro during the course of treatment; and wherein (1)the subject undergoes heightened monitoring for an allergic reaction ifthe level of peanut-specific IgEs in the subject rises above thepredetermined threshold during the course of treatment; or (2) a dose ofthe allergenic peanut composition is reduced, a dose of the allergenicpeanut composition administered to the subject is delayed, or anincrease of a dose of the allergenic composition is delayed if the levelof peanut-specific IgEs in the subject rises above the predeterminedthreshold during the course of treatment.

Embodiment 235

An allergenic peanut composition for use in treating a subject for apeanut allergy, wherein at least one dose of the allergenic peanutcomposition is administered to the subject, and wherein the subjectundergoes heightened monitoring for an allergenic reaction if a level ofpeanut-specific IgEs in the subject is above a predetermined threshold.

Embodiment 236

Use of an allergenic peanut composition in the manufacture of amedicament for use in treating a subject for a peanut allergy, whereinat least one dose of the allergenic peanut composition is administeredto the subject, and wherein the subject undergoes heightened monitoringfor an allergenic reaction if a level of peanut-specific IgEs in thesubject is above a predetermined threshold.

EXAMPLES

The application may be better understood by reference to the followingnon-limiting examples, which are provided as exemplary embodiments ofthe application. The following examples are presented in order to morefully illustrate embodiments and should in no way be construed, however,as limiting the broad scope of the application. While certainembodiments of the present application have been shown and describedherein, it will be obvious that such embodiments are provided by way ofexample only. Numerous variations, changes, and substitutions may occurto those skilled in the art without departing from the spirit and scopeof the invention. It should be understood that various alternatives tothe embodiments described herein may be employed in practicing themethods described herein.

Example 1: Treatment of a Patient Allergic to Peanuts

A peanut allergic patient would be screened according to the methodsdescribed above. If the patient is likely to respond favorably to theoral administration of escalating doses of peanut allergens, then thepatient would be treated according to protocol set forth below. If thepatient is unlikely to respond favorably to the oral administration ofescalating doses of peanut allergens, then the patient would not receivea medical intervention. An exemplar treatment protocol for treating apeanut allergy patient with oral immunotherapy (OIT) is shown in FIG. 2.

Exemplary Treatment Protocol for Treating a Peanut Allergy Patient withOIT:

Initial Escalation (2 Days):

Eligible subjects will initiate OIT starting at a dose of 0.5 mg ofpeanut protein, and then increase the dose incrementally at 20 to 30minute intervals over the course of a single day to a maximum dose of 6mg. Subjects who fail to tolerate at least a 3 mg dose will beconsidered escalation failures. Subjects who tolerate both the 3 mg and6 mg doses of study product, or who tolerate the 3 mg, but not the 6 mgdose, will undergo confirmatory testing of the tolerability of a 3 mgdose the following day (see Initial Escalation Schedule below).

Up-Dosing:

Subjects will receive daily oral dosing of peanut or placebo OIT forabout 5 months (20 weeks, if up-dosing proceeds without holding at, orreducing, a dose level; 40 weeks, maximum). All escalation doses (seeescalation table below) will occur in a clinical research center (CRC)or other monitored setting (unless required by a specific institution,no distinction will be drawn between an investigational site, studycenter office, clinic, or CRC, provided the capability requirements formonitoring and emergency intervention are met by the facility). Allup-dosing activities will be performed under the direct observation.

Maintenance:

Those subjects who reach the target maintenance dose of 300 mg/d ofstudy product will enter an approximately 24-week Maintenance Period ofcontinued dosing at 300 mg/d.

TABLE 1 Initial Escalation Period, Day-1, Dosing Schedule Study ProductDose Day-1 (mg peanut protein Cumulative Study Product Dose Dose # orplacebo) (mg peanut protein or placebo) 1 0.5 0.5 2 1 1.5 3 1.5 3 4 3 65 6 12

TABLE 2 Up-dosing Period Dosing Schedule Study Product Dose Up-dosing(mg peanut protein Dose # or placebo) Interval (weeks) % Increase 1 3 22 6 2 100% 3 12 2 100% 4 20 2 67% 5 40 2 100% 6 80 2 100% 7 120 2 50% 8160 2 33% 9 200 2 25% 10 240 2 20% 11 300 24-Week Maintenance 25% Period

Example 2: Treatment of a Peanut Allergy Patient Unlikely to RespondFavorably to the Oral Administration of Escalating Doses of PeanutAllergens

A peanut allergic patient would be screened according to the methodsdescribed above. If the patient is likely to respond favorably to theoral administration of escalating doses of peanut allergens, then thepatient would be treated according to the protocol set forth inExample 1. If the patient is unlikely to respond favorably to the oraladministration of escalating doses of peanut allergens, then the patientwould be treated with omalizumab before and/or during the OIT treatmentprotocol set forth in Example 1.

Example 3: Detection of Peanut-Specific IgE in a Subject

Blood samples are collected from subjects seeking oral immunotherapy fora peanut allergy and stored at about 4° C. for same week processing orabout −20° C. for longer-term storage. The blood samples are transportedto a facility with an immunoautoanalyser or similar device forquantitative immunoassay. Immunoassay solid phases comprising peanutprotein extract are prepared. Blood samples are processed and injectedonto the solid phase for assay following manufacturer or known protocolsfor capture of peanut-specific IgE from subject serum or plasma. Afterwashing of the solid phase, anti-IgE antibodies comprising a fluorescentmoiety are added to the solid phase. After washing, a developing reagentis added to the solid phase and incubated. The developing reaction isstopped and fluorescent readings are correlated to serum concentrationbased on comparison to a commercial control. Concentrations are reportedin units of kU/L. The subject's peanut-specific IgE level is received bythe subject's medical practitioner.

Example 4: Oral Immunotherapy in Subjects Presenting Symptoms

Subjects undergoing an oral immunotherapy dosage regimen for treatmentof a known peanut allergy who present symptoms similar to an allergenicreaction, including but not limited to gastrointestinal distress,anaphylaxis, or eosinophilic esophagitis, have a level ofpeanut-specific IgEs measured. Blood samples are collected, serialdiluted if necessary, processed, and assayed from the subject forpeanut-specific IgE as described in Example 3. The facility processingthe blood sample reports a peanut-specific IgE level to a clinician. Ifthe level of peanut-specific IgE exceeds 100 kU/L, the cliniciansuspends administration of the oral immunotherapy dosage. After a 30 daydelay, administration of the oral immunotherapy dosage is resumed.

Example 5: Heightened Monitoring of a Subject in Response to a Level ofPeanut-Specific IgEs

A level of peanut-specific IgEs is measured in a subject seeking oralimmunotherapy. Blood samples are collected from the subject, serialdiluted if necessary, processed, and assayed for peanut-specific IgEserum concentration as described in Example 3. The facility processingthe blood sample reports a peanut-specific IgE level to a clinician. Ifthe level of peanut-specific IgE is equal to or less than a thresholdvalue of 100 kU/L, the subject begins a normal course of oralimmunotherapy under standard medical supervision. If the subject's levelof peanut-specific IgEs exceeds a threshold value of 100 kU/L, theclinician will administer the oral immunotherapy dosage to the subjectwhile increasing monitoring of the subject relative to the subject witha level of peanut-specific IgEs at or below the threshold. Heightenedmonitoring can include at least weekly testing of a level ofpeanut-specific IgEs; active monitoring for symptoms of an allergicreaction (such as hypersensitivity, anaphylaxis, gastrointestinalsymptoms, or eosinophilic esophagitis) in a clinical setting afteradministration of the dose of the allergenic peanut composition, whichmay be for a longer monitoring period than for a subject with a level ofpeanut-specific IgEs below the predetermined threshold; or monitoring ofheart rate and/or respiratory rate of the subject for a period of timeafter administration of the dose of the allergenic peanut composition.

Example 6: Reducing the Risk or Incidence of an Adverse Event in aSubject Receiving Treatment for a Peanut Allergy

A level of peanut-specific IgEs is measured in a subject being treatedfor a peanut allergy using oral immunotherapy. Blood samples arecollected from the subject, serial diluted if necessary, processed, andassayed for peanut-specific IgE serum concentration as described inExample 3. The facility processing the blood sample reports a level ofpeanut-specific IgEs to a clinician. If the level of peanut-specificIgEs is equal to or less than 100 kU/L, the subject is cleared tomaintain the standard course and schedule of oral immunotherapy, absentother indications to the contrary. If the subject's level ofpeanut-specific IgEs exceeds a threshold value of 100 kU/L, the nextdose can be reduced or delayed.

Example 7

Introduction. Two phase 2 trials (ARC001, and its follow-on ARC002)previously demonstrated evidence of efficacy and tolerability of AR101,a pharmaceutical-grade peanut-flour-derived CODIT formulation, indesensitizing peanut-allergic subjects.

Methods. Children and adult subjects with peanut allergy confirmed bydouble-blind placebo-controlled food challenge (DBPCFC), participated inARC001, a double-blind placebo-controlled trial (active n=29, placebon=26), and were followed in ARC002, an open label trial (active n=47).The AR101 updosing period (from 3 mg/d to 300 mg/d) was followed by a12-week maintenance period (300 mg/d). Peanut skin prick test (SPT) andpeanut-specific (ps) IgE (Immulite©, upper quantification limit of 100kU_(A)/L) were performed at baseline, before randomization. Aretrospective cohort analysis was performed to evaluate the safety andefficacy profile of AR101.

Results. In a preliminary analysis of the 55 treated patients based onpsIgE, 23 had a baseline ps-IgE level of <100 kU/L, 25 patients had abaseline ps-IgE level of >100 kU/L, and data was unavailable for 7patients during the preliminary analysis. See FIGS. 1A-C. Across allpeanut allergic patients (not those limited to the phase 2 study), it isgenerally determined that 80% of patients have an IgE level of less than100 kU/L, and 20% had a ps-IgE level of more than 100 kU/L.Additionally, 100% of intent-to-treat (ITT) patents and 100% ofcompleters with a ps-IgE level lower than 100 kU/L were able to tolerate443 mg of peanut protein after up-dosing. However, of those patientswith ps-IgE level >100 kU/L, only 56% of ITT patients and 93% ofcompleters tolerated 443 mg of peanut protein post up-dosing.Additionally, those with a ps-IgE level lower than 100 kU/L had a 0%dropout rate from the study, whereas those patients with a ps-IgE levelhigher than 100 kU/L had a 40% dropout rate from the study. At entry ofthe study, the mean skin prick test (SPT) for those patients with aps-IgE level of less than 100 kU/L was 15 mm, and the mean SPT for thosepatients with a ps-IgE level of more than 100 kU/L was 13 mm. The meantolerated dose at entry for patients with a ps-IgE level of less than100 kU/L was 20 mg, and the mean tolerated dose for those patients witha ps-IgE level of more than 100 kU/L was 16 mg. Generally, patients whodon't achieve robust reliable efficacy on OIT are those who cannottolerate it based on GI symptoms. This will be better understood byphase 3 trials.

Of the 55 patients starting ARC001, baseline psIgE was very high (>100kU_(A)/L) in 28 patients, and lower (≤100 kU_(A)/L) in 27 patients. Inthe lower baseline psIgE group, there were no treatment-relatedwithdrawals and all patients met the primary endpoint at the exitDBPCFC. However, in the very high baseline psIgE group (>100 kU_(A)/L),10 of 28 patients (36%) withdrew due to treatment-related adverse events(gastrointestinal symptoms ranging from oral pruritus to moderatevomiting and/or abdominal pain), and one patient failed the exit DBPCFC.Baseline peanut SPT and screening DBPCFC results were not clinicallydifferent between these two groups (≤100 kU_(A)/L vs >100 kU_(A)/Lbaseline psIgE).

Conclusions. In two phase 2 trials, baseline peanut-specific IgE levelappears to be predictive of up-dosing completion and treatment responsewith AR101 in CODIT, as well as a meaningful reduction in drop-out ratefrom up-dosing and a lower risk for GI symptoms.

Example 8: Oral Immunotherapy for the Treatment of a Peanut AllergyStudy Design

The following study was conducted as a multicenter, double-blind,placebo-controlled phase 3 trial was conducted at 66 sites in 10countries. Patients aged 4-55 years were considered eligible. Allparticipants had a clinical history of peanut allergy, confirmed byscreening DBPCFC, and either serum peanut-specific IgE (psIgE) ≥0.35kU_(A)/L by ImmunoCAP™ (Thermo Fisher Scientific, Waltham Mass.) and/orpeanut skin prick test mean wheal diameter ≥3 mm larger than thenegative control at screening. Key exclusion criteria included a historyof medically significant chronic or recurrent gastrointestinal symptomsof any etiology, including eosinophilic esophagitis (EoE); severe oruncontrolled asthma using National Heart, Lung, and Blood Institutedefinitions; or the use of a prohibited medication. Patients with ahistory of severe/life-threatening anaphylaxis were permitted, if theepisode occurred ≥60 days before screening. Patients living at the sameaddress were excluded from the trial to minimize the chances ofinadvertent unblinding or errant administration of the incorrectinvestigational product. At the end-of-study visit, the exit DBPCFC wasto be independently assessed by a physician at the site experienced inthe procedure who had not substantially participated in the care of thatparticipant throughout the trial.

Initial Enrollment:

842 Individuals were screened by double blind placebo controlled foodchallenge (DBPCFC) for allergy to peanut. Individuals who wereintolerant of 30 mg or less of peanut protein were enrolled in thestudy. Individuals who tolerated more than 30 mg of peanut protein wereexcluded. 551 enrolled individuals were divided 3:1 into peanut proteinoral immunotherapy (OIT) and placebo arms. 413 individuals receivedpeanut protein OIT and 138 individuals received placebo. The studypopulation averaged 11.3 years of age (range 4-55), was 57% male, and80% Caucasian. 407 (74%) had a history of peanut anaphylaxis prior toscreening, 53% had asthma, 66% had multiple food allergies, and 43% hadpeanut-specific IgE levels greater than or equal to 100 kU/L. Baselinemedian (IQR) values were as follows: peanut skin prick wheal diameter11.5 (range 9-15) mm; and peanut specific IgE 61.75 (range 16.7-179)kU/L. Of the total study population, 496 were 4-17 years of age. Of the4-17-year-old age group, 372 individuals received the peanut proteinOIT, and 124 individuals received placebo.

Administration:

Both peanut protein and placebo, which were similar in appearance, wereadministered as a powder in graduated doses provided in pull-apartcapsules (0.5, 1, 10, 20, or 100 mg) or foil-laminate sachets (300 mg),according to the procedure described below, and formulated with bulkingand flow agents considered generally recognized as safe. Capsules (orsachets) were opened and the content mixed thoroughly with a fewspoonfuls of age-appropriate, non-allergenic food, and generallyconsumed within 4 hours.

Up-Dosing Phase:

The total treatment duration was approximately twelve months and wasdivided into two phases. During the up-dosing phase, which lastedapproximately six months, OIT recipients began receiving daily 3 mgdoses of peanut protein and ended the phase receiving daily 300 mg dosesof peanut protein, with dose escalations occurring every two weeks. Theup-dosing phase consisted of this biweekly progression through the 3, 6,12, 20, 40, 80, 120, 160, 200, and 240 mg dose levels and could take nomore than 40 weeks. All dose escalations occurred in a clinical researchcenter (CRC) or other monitored setting with emergency interventioncapabilities. Daily doses were self-administered by the individual athome.

Maintenance Phase:

During the second phase, termed the maintenance phase, which lastedapproximately six months, OIT recipients received daily 300 mg doses ofpeanut protein which they self-administered at home.

Completion:

At the end of the maintenance phase or upon study exit, participantsfrom both the OIT and placebo arms underwent a DBPCFC and blood test.

Results

General:

No deaths or suspected, unexpected serious adverse reactions (SUSARs)were observed. Incidence of reported serious adverse events (SAEs) waslow in both arms for the 4-17-year-old age group, with 9 patients in theOIT arm (2.4%) reporting a SAE, 4 of which were possibly-related totreatment (1.1%). Of these 4 patients, 2 experienced severe events,including 1 case of anaphylaxis and 1 case of wheezing. Both of thesepatients had initial peanut-specific IgE levels greater than 100 kU/L.One patient in the placebo arm was reported to experience a seriousadverse event. Over 85% of the OIT patients did not experience systemichypersensitivity reactions. Of the 14.5% who did experiencehypersensitivity reactions, 98.2% had mild or moderate reactions.

Completion Rate in Ages 4-17:

As indicated in Table 3 below, approximately 80% of individuals in the4-17 year-old OIT arm completed the study. In this arm, 16.7% of thetotal 4-17 year old group discontinued during the up-dosing phase, and3.8% during the maintenance phase. One individual discontinued the studydue to biopsy-confirmed moderate, non-serious eosinophilic esophagitis(EoE) during the study. No additional cases of EoE were identified inthe study. Of the systemic hypersensitivity reactions, seven wereinvestigator-identified anaphylaxis events (six mild, one severe). Thefour additional individuals discontinued the study for acute viralillness, eye pruritus, headache, or an unknown factor.

TABLE 3 Peanut Protein OIT for Individuals Ages 4-17 Percent totalNumber of OIT arm individuals Total discontinuations regardless of 20.4%76 causality Discontinuations not related to 8.0% 30 adverse eventsDiscontinuations related to adverse 12.4% 46 events Gastrointestinal6.7% 25 Systemic hypersensitivity 2.7% 10 reactions Respiratory system1.1% 4 Cutaneous 0.8% 3 Other 1.1% 4

Intent-to-Treat Efficacy in Total Study:

The intent-to-treat group includes all individuals enrolled in eitherthe OIT or placebo arms of the study, regardless of treatment adherence,withdrawal from the study, or deviation from the study design. As shownin Table 4, of the 413 individuals in the OIT arm, 73.4% successfullytolerated a 300 mg peanut protein dose in a DBPCFC upon exit from thestudy, 64.6% successfully tolerated a 600 mg dose in a DBPCFC upon exitfrom the study, and 48.7% successfully tolerated a 1,000 mg dose in aDBPCFC upon exit from the study. In contrast, only 10.9% of placebo armindividuals successfully tolerated a 300 mg dose in a DBPCFC upon exitfrom the study, 5.1% successfully tolerated a 600 mg dose in a DBPCFCupon exit from the study, and 3.6% tolerated a 1,000 mg dose in a DBPCFCupon exit from the study. The 95% confidence interval and p-value wascalculated as indicated for each dose level.

TABLE 4 300 mg 600 mg 1,000 mg OIT Arm (n = 413) 73.4% 64.6% 48.7%Placebo (n = 138) 10.9%  5.1%  3.6% 95% CI difference (53-72%)(49.9-69.2%) (35.7-54.4%) p-value p < 0.00001 p < 0.00001 p < 0.00001

Intent-to-Treat Efficacy in 4-17 Year Olds:

This intent-to-treat group of 4-17 year old study participants includesall 4-17 year old individuals enrolled in either the OIT or placebo armsof the study, regardless of treatment adherence, withdrawal from thestudy, or deviation from the study design. As shown in Table 5, of the372 individuals in the OIT arm, 76.6% successfully tolerated a 300 mgpeanut protein dose in a DBPCFC upon exit from the study, 67.2%successfully tolerated a 600 mg dose in a DBPCFC upon exit from thestudy, and 50.3% successfully tolerated a 1,000 mg dose in a DBPCFC uponexit from the study. In contrast, only 8.1% of placebo arm individualssuccessfully tolerated a 300 mg dose in a DBPCFC upon exit from thestudy, 4.0% successfully tolerated a 600 mg dose in a DBPCFC upon exitfrom the study, and 2.4% tolerated a 1,000 mg dose in a DBPCFC upon exitfrom the study. The 95% confidence interval and p-value was calculatedas indicated for each dose level.

TABLE 5 300 mg 600 mg 1,000 mg OIT Arm (n = 372) 76.6% 67.2% 50.3%Placebo (n = 124)  8.1%  4.0%  2.4% 95% CI Difference (58.6-78.5%)(53.0-73.3%) (38.0-57.7%) p-value p < 0.00001 p < 0.00001 p < 0.00001

Further, as indicated in FIG. 3, the median amount of peanut proteintolerated in entry and exit peanut challenges for the intent-to-treatpopulation was significantly different between study arms.

Completer Efficacy:

The completer population includes all individuals enrolled who completedsubstantially all of the full approximately twelve month study. As shownin Table 6, of the 316 completers in the OIT arm, 95.9% successfullytolerated a 300 mg dose in a DBPCFC upon exit from the study, 84.5%successfully tolerated a 600 mg dose in a DBPCFC upon exit from thestudy, and 63.6% successfully tolerated a 1,000 mg dose in a DBPCFC uponexit from the study. In contrast, only 11.6% of placebo arm individualssuccessfully tolerated a 300 mg dose in a DBPCFC upon exit from thestudy, 5.4% successfully tolerated a 600 mg dose in a DBPCFC upon exitfrom the study, and 3.9% tolerated a 1,000 mg dose in a DBPCFC upon exitfrom the study. The 95% confidence interval and p-value was calculatedas indicated for each dose level.

TABLE 6 300 mg 600 mg 1,000 mg OIT Arm (n = 316) 95.9% 84.5% 63.6%Placebo (n = 129) 11.6%  5.4%  3.9% 95% CI Difference (75.0-93.5%)(69.1-89%) (49.5-69.9%) p-value p < 0.00001 p < 0.00001 p < 0.00001

Completer Efficacy in 4-17 Year Olds:

This group includes all 4-17 year old individuals enrolled who completedsubstantially all of the full approximately twelve month study. As shownin Table 7, of the 296 completers in the OIT arm, 96.3% successfullytolerated a 300 mg dose in a DBPCFC upon exit from the study, 84.5%successfully tolerated a 600 mg dose in a DBPCFC upon exit from thestudy, and 63.2% successfully tolerated a 1,000 mg dose in a DBPCFC uponexit from the study. In contrast, only 8.6% of placebo arm individualssuccessfully tolerated a 300 mg dose in a DBPCFC upon exit from thestudy, 4.3% successfully tolerated a 600 mg dose in a DBPCFC upon exitfrom the study, and 2.6% tolerated a 1,000 mg dose in a DBPCFC upon exitfrom the study. The 95% confidence interval and p-value was calculatedas indicated for each dose level.

TABLE 7 300 mg 600 mg 1,000 mg OIT Arm (n = 296) 96.3% 84.5% 63.2%Placebo (n = 116)  8.6%  4.3%  2.6% 95% CI Difference (78.0-97.3%)(69.7-90.6%) (49.9-71.3%) p-value p < 0.00001 p < 0.00001 p < 0.00001

Symptom Severity at Exit Peanut Challenge for 4-17 Year Olds:

Among the 4-17 year old completer population, the severity of symptomsbetween the OIT and placebo arms was observed during the exit DBPCFC. Asshown in FIG. 4, the OIT arm developed far fewer moderate and severesymptoms as compared to the placebo arm. The number of individualspassing the food challenge at the indicated dose is indicated by theblack diamond.

Treatment-Emergent Adverse Events for 4-17 Age Group:

The treatment-emergent adverse events (TEAE) profile was observed forthe 4-17 age group of both arms. As Table 8 below indicates, the TEAEprofile was similar for both the OIT and placebo arms.

TABLE 8 OIT Placebo Mild/ Mild/ Moderate Severe Moderate Severe Subjectsreporting at 94.1%   4.6% 92.7%   2.4% least one TEAE Gastrointestinal84% 1.3% 69% 0.8% Respiratory, thoracic, 80% 0.8% 72% 0.0% andmediastinal Infections and 70% 0.3% 73% 0.0% infestations Skin andsubcutaneous 66% 1.3% 55% 0.0% tissue General disorders and 37% 0.0% 31%0.0% administration site conditions Nervous system 26% 0.3% 26% 0.0% Eye20% 0.3% 21% 0.0% Immune system 17% 0.3%  9% 1.6% Injury, poisoning, and15% 0.0% 23% 0.0% procedural complications Vascular 13% 0.3%  2% 0.0%Ear and labyrinth 13% 0.3%  2% 0.0% Musculoskeletal and  8% 0.0% 10%0.0% connective tissue Psychiatric  5% 0.0%  2% 0.0%

Age Profile of Completer Population:

As indicated in FIG. 5, patients across age cohorts (i.e., ages 4-11,12-17, and 18-55 years old) responded similarly to the peanut proteinOIT as measured by tolerance to a 600 mg peanut protein dose during anexit DBPCFC. 600 mg of peanut protein is approximately equivalent to thepeanut protein in two whole peanuts.

Measurement of Peanut-Specific IgE in 4-17 Year Olds:

Patients 4-17 years old had their peanut-specific IgE serum levelsmeasured at the beginning of therapy, prior to administration of thefirst dose. As shown in Table 9 below, 4-17-year-old patients withstarting peanut-specific IgE levels less than or equal to 100 kU/L,after one year of OIT (6 months up-dosing phase and 6 months ofmaintenance phase), were more likely to become tolerant of a 1,000 mgpeanut protein dose during the completion DBPCFC, were less likely todiscontinue due to gastrointestinal adverse events, and were less likelyto have a severe hypersensitivity reaction as compared with individualswith a starting peanut-specific IgE level greater than 100 kU/L.

TABLE 9 Intent-to-treat population Completer population Peanut-specificPeanut-specific Peanut-specific Peanut-specific Patient Outcomes, IgE≤100 kU/L IgE >100 kU/L IgE ≤ 100 kU/L IgE > 100 kU/L N (%) (N = 213) (N= 159) (N = 176) (N = 120) Tolerated 1,000 mg 117 (55%) 70 (44%) 117(67%) 70 (58%) dose Discontinued due 10 (5)    15 (9%)  N/A N/A togastrointestinal adverse events Experienced a 0   1 (0.6%) N/A N/Asevere systemic hypersensitivity reaction

Immune Modulation in Patients Age 4-17:

Patients 4-17-years-old receiving the peanut protein OIT demonstratedmarked immune modulation. As shown in FIG. 6A, OIT patients displayedincreased peanut-specific IgE levels during the up-dosing phase, whilethey experienced ongoing reductions in peanut-specific serum IgE levelsduring the maintenance phase. Placebo group peanut-specific serum IgElevels did not change appreciably over the year of study. Further, asshown in FIG. 6B, the ratio of peanut-specific IgE to IgG4 (IgE/IgG4ratio) changed dramatically over the course of the study for the OITrecipients, while no decrease was observed for the placebo group. Asshown in FIG. 6C, OIT recipients displayed weaker response to the skinprick test as measured by mean wheal diameter above negative control.Finally, as shown in FIG. 6D, peanut-specific IgG4 increased during thecourse of the study for the OIT recipients, whereas peanut-specific IgG4levels remained approximately stable for recipients of the placeboformulation. These data are also reported in Table 10 below.

TABLE 10 End of Baseline Up-dosing End of Study OIT Placebo OIT PlaceboOIT Placebo P-value Peanut Skin 12.0 12.7 7.8 11.4 7.5 (3.4) 11.8 (5.6)<0.0001 Prick Test (mm) (4.9) (5.7) (3.7) (4.6) n = 371 n = 124 n = 304n = 116 n = 292 n = 115 psIgE (kUA/L) 52.0 62.7 101.3 78.8 48.6 (7.8) 76.1 (6.9) 0.5044 (6.1) (6.2) (8.1) (7.2) n = 371 n = 121 n = 305 n =116 n = 272 n = 104 psIgG4 (mgA/L) 0.5 0.6 3.3 0.6 5.6 (4.5)  0.6 (3.0)<0.0001 (3.5) (3.4) (4.0) (2.8) n = 353 n = 116 n = 305 n = 116 n = 274n = 104 psIgE/psIgG₄ 97.6 111.9 30.3 124.1 8.8 (5.3) 129.3 (6.5) <0.0001 (5.1) (6.3) (4.6) (6.8) n = 353 n = 115 n = 305 n = 116 n = 272n = 104

Epinephrine Usage.

It was further observed that baseline peanut-specific IgE levels were agood indicator for assessing the likelihood of a patient experiencing anallergic reaction requiring the use of epinephrine. Specifically, themean baseline psIgE in patients receiving the peanut OIT that had anallergic reaction requiring the use of epinephrine was 266 kU/L, whereasthe mean baseline psIgE in patients receiving OIT that did not have anallergic reaction requiring the use of epinephrine was 72 kU/L.

All document disclosed herein are incorporated by reference in theirentirety for all purposes.

1. A method of treating a subject for a peanut allergy, comprising:administering to the subject at least one dose of an allergenic peanutcomposition, wherein the subject is selected for treatment based onhaving a level of peanut-specific IgEs at or below a predeterminedthreshold.
 2. The method of claim 1, wherein the predetermined thresholdfor the level of peanut-specific IgEs is about 100 kU/L.
 3. The methodof claim 2, wherein the level of peanut-specific IgEs is determinedprior to initiating treatment of the peanut allergy.
 4. The method ofclaim 2, wherein the does is administered to the subject as part of anoral immunotherapy dosing regimen.
 5. The method of claim 4, wherein thedose is administered to the subject during an initial escalation phaseof the oral immunotherapy dosing regimen.
 6. The method of claim 4,wherein the dose is administered to the subject during an up-dosingphase of the oral immunotherapy dosing regimen.
 7. The method of claim4, wherein the dose is administered to the subject during a maintenancephase of the oral immunotherapy dosing regimen.
 8. The method of claim2, comprising receiving the level of peanut-specific IgEs.
 9. The methodof claim 2, comprising measuring the level of peanut-specific IgEs. 10.A method of treating a subject for a peanut allergy, comprising:administering to the subject at least one dose of an allergenic peanutcomposition, wherein the subject undergoes heightened monitoring for anallergenic reaction if a level of peanut-specific IgEs in the subject isabove a predetermined threshold. 11-23. (canceled)
 24. A method ofassessing the suitability of a treatment for a peanut allergy in asubject, comprising: receiving a level of peanut-specific IgEs in thesubject; and assessing the suitability of the treatment, wherein thesubject having a level of peanut-specific IgEs at or below apredetermined threshold indicates that the treatment is suitable for thesubject. 25-29. (canceled)
 30. A method of evaluating a symptom in asubject during the course of treatment of a peanut allergy, comprising:receiving a level of peanut-specific IgEs in the subject having anadverse event; and determining whether the symptom is related to thetreatment, wherein a level of peanut-specific IgEs at or below apredetermined threshold indicates that the adverse event is not causedby the treatment. 31-41. (canceled)
 42. A method of monitoring treatmentfor a peanut allergy in a subject, comprising: measuring a level ofpeanut-specific IgEs in the subject during the course of treatment. 43.The method of claim 42, wherein the treatment is an oral immunotherapydosage regimen.
 44. The method of claim 42, comprising reducing ordelaying a dose of an allergenic peanut composition if the level ofpeanut-specific IgEs is above a predetermined threshold.
 45. The methodof claim 42, comprising delaying a dose increase during an up-dosingphase of the treatment if the level of peanut-specific IgEs is above apredetermined threshold.
 46. The method of claim 42, comprisingterminating the treatment if the level of peanut-specific IgEs is abovea predetermined threshold.
 47. The method of claim 42, comprisingincreasing the dose if the level of peanut-specific IgEs is at or belowa predetermined threshold.
 48. The method of claim 44, wherein thepredetermined threshold is about 100 kU/L.
 49. The method of claim 42,wherein the level of peanut-specific IgEs is measured following aninitial escalation phase of the treatment.
 50. The method of claim 42,wherein the level of peanut-specific IgEs is measured during anup-dosing phase of the treatment.
 51. The method of claim 42, whereinthe level of peanut-specific IgEs is measured during a maintenance phaseof the treatment.
 52. A method of reducing the risk or incidence of anadverse event in a subject receiving treatment for a peanut allergy,comprising: receiving a level of peanut-specific IgEs in the subject;and reducing a dose, delaying a dose, or delaying an increase of a doseof an allergenic peanut composition if the level of peanut-specific IgEsis above a predetermined threshold.
 53. The method of claim 52, whereinthe treatment is oral immunotherapy.
 54. The method of claim 52, whereinthe predetermined level of the peanut-specific IgEs is about 100 kU/L.55. The method of claim 54, comprising measuring the level ofpeanut-specific IgEs in the subject.
 56. The method of claim 54, whereinthe adverse event is an allergic reaction.
 57. The method of claim 54,comprising reducing the dose of the allergic peanut composition if thelevel of peanut-specific IgEs is above the predetermined threshold. 58.The method of claim 57, wherein the dose of the allergenic peanutcomposition is reduced during an up-dosing phase of the treatment. 59.The method of claim 57, wherein the dose of the allergenic peanutcomposition is reduced during a maintenance phase of the treatment. 60.The method of claim 54, comprising delaying the dose of the allergicpeanut composition if the level of peanut-specific IgEs is above thepredetermined threshold.
 61. The method of claim 60, wherein the dose isdelayed during an up-dosing phase of the treatment.
 62. The method ofclaim 60, wherein the dose is delayed during a maintenance phase of thetreatment.
 63. The method of claim 54, comprising delaying the increaseof the dose of the allergic peanut composition during an up-dosing phaseof the therapy if the level of peanut-specific IgEs is above thepredetermined threshold.
 64. The method of claim 54, comprisingadministering the dose to the subject.
 65. A method of adjusting a doseof an allergenic peanut composition, comprising: administering a firstdose of the allergenic peanut composition to a subject with a peanutallergy; receiving a level of peanut-specific IgEs in the subject afteradministration of the first dose; and administering a second dose of theallergenic peanut composition to the subject, wherein the second dose isbased on the first dose and the level of peanut-specific IgEs in thesubject. 66-71. (canceled)
 72. A method of monitoring treatment for apeanut allergy in a subject, comprising: measuring a level ofpeanut-specific IgG4s or a peanut-specific IgE to peanut-specific IgG4ratio in the subject during the course of treatment. 73-78. (canceled)79. The method of claim 42, wherein the subject is a human.
 80. Themethod of claim 42, wherein the subject is about 17 years of age oryounger.
 81. The method of claim 80, wherein the subject is about 4years of age to about 17 years of age.
 82. The method of claim 48,wherein the level of peanut-specific IgEs corresponds to a level asmeasured by a fluorescence enzyme immunoassay auto-analyzer.
 83. Themethod of claim 48, wherein the level of peanut-specific IgEs ismeasured by a fluorescence enzyme immunoassay auto-analyzer. 84-126.(canceled)